β-Amyloid formation by myocytes of leptomeningeal vessels

Ultrastructural study of the leptomeningeal vessels of three subject with Alzheimer's disease (AD) shows that -amyloid deposits in the media of arteries and arterioles are produced by smooth muscle cells. It appears that the soluble -protein secreted by sarcolemmal vesicles of the muscle cell polymerizes into amyloid fibrils in basal lamina. Myocytes trapped in amyloid deposits degenerate and die. The most common and severe degeneration of smooth muscle cells in seen in the external and medial zone of the vascular media. In more advanced stages of amyloidotic changes, the internal zone of media is also involved. The media of vessels with severe changes consists of amyloid deposits and cell debris. Amyloid fibrils around the dead myocytes also undergo degradation. They lose their fibrillar appearance and become floccular, granular, amorphous proteinous material; however, this material is continually positive in immunostaining for -amyloid. This study suggests that amyloid formation by smooth muscle cells involves a secretory path. Our data indicate that the smooth muscle cell secretes nonfibrillar -protein or -protein containing peptides and that conversion of nonfibrillar into fibrillar -amyloid takes place in the environment of the basement membrane.Supported in part by funds from the New York State Office of Mental Retardation and Developmental Disabilities and a grant from the National Institutes of Health, National Institute of Aging No. PO1-AGO-4220     

Types of authority and two problems of psychiatric wards

This paper concerns the relationship between authority structures and two problems reported in the literature as common to milieu or therapeutic community wards. Psychiatric wards with rational-legal and charismatic authority structures are found more likely to experience mood and morale swings on the part of patients and staff and to spend excessive time and energy changing ward rules.     

Clinical, histological, and immunohistochemical features predicting 1p/19q loss of heterozygosity in oligodendroglial tumors

To identify a better diagnostic criteria for oligodendroglial tumors, we investigated the clinical, histological, and immunohistochemical features that would be able to predict a 1p/19q loss of heterozygosity (LOH) in these tumors. We performed a PCR-based LOH test with the 1p and 19q microsatellite markers by microdissecting tumor in 56 samples (44 oligodendrogliomas and 12 mixed oligoastrocytomas) of paraffin-embedded tissue. Patients with oligodendroglial tumors with 1p/19q LOH had a statistically significant better prognosis for overall survival. Comparative analysis of several features indicated that the 1p/19q LOH tumors were associated with two histological features, tumor cellularity and perinuclear halo, and low O⁶-methylguanine-DNA-methyltransferase (MGMT) expression and high cytoplasmic glutathione S-transferase pi (GST-) expression. In addition, the incidence of 1p/19q LOH was infrequent in the youngest age category (less than 20 years old) studied. Using the new features, we could predict the 1p/19q status of oligodendroglial tumors with greater than 90% accuracy. Therefore, applying these features in clinical practice, would be helpful in clarifying oligodendroglial tumor diagnosis.     

Herpes simplex virus persistence in mouse neuroblastoma (C 1300) cell cultures: Role of interferon

Summary The Mp strain of herpes simplex virus type 1 (HSV₁) induced a persistent infection in the mouse C 1300 neuronal cell line (clone N 115). C 1300 cultures infected at an MOI of 0.01 or 0.001 survived the initial infection and continued to produce infectious virus and viral antigens for 185 days and 31 days, respectively. Viral antigens were not detected in cultures no longer producing infectious virus; these cured cultures had comparable susceptibility to reinfection with HSV as previously uninfected C 1300 cells. While significant amounts of interferon were produced by C 1300 cells when challenged with Newcastle Disease Virus (NDV) or when treated with poly I:C, HSV-induced interferon could not be detected in either the acutely or persistently infected cell lines. The persistent state was not significantly altered by the addition of 1,000 units/ml of murine interferon alpha plus beta (MuIFN+), nor was it affected by the addition of antibody to MuIFN. It appears that IFN does not play an important role in the establishment and/or maintenance of viral persistence in this neuronal system.     

The Diverse Roles of Anticonvulsants in Bipolar Disorders

Anticonvulsant drugs (ACs) have diverse antiseizure, psychotropic, and biochemical effects. Carbamazepine and valproate have mood-stabilizing actions, benzodiazepines and gabapentin have anxiolytic actions, lamotrigine is useful in rapid cycling and acute treatment and prophylaxis of bipolar depression, and topiramate and zonisamide can yield weight loss. Limited controlled data suggest the carbamazepine keto derivative oxcarbazepine has antimanic effects. A categorical approach to the diverse roles of ACs in bipolar disorders is proposed, using broad categories of ACs, on the basis of their predominant psychotropic profiles. Thus, some ACs have sedating profiles that may include sedation, cognitive difficulties, fatigue, weight gain, and possibly antimanic and/or anxiolytic effects. In contrast, some newer ACs have activating profiles that may include improved energy, weight loss, and possibly antidepressant and even anxiogenic effects. Still other newer ACs have novel mixed profiles, combining sedation and weight loss. A categorical–mechanistic extension of this approach is also presented, with hypotheses that sedating profiles might be related to prominent potentiation of gamma-aminobutyric acid (GABA) inhibitory neurotransmission, activating profiles could be related to prominent attenuation of glutamate excitatory neurotransmission, and for mixed profiles, sedation and weight loss might be related to concurrent GABAergic and antiglutamatergic actions, respectively. The categorical approach may have utility as an aid to clinicians in reinforcing the heterogeneity ACs, and recalling psychotropic profiles of individual ACs, but is limited as it fails to address the etiology of the heterogeneity of AC psychotropic effects. The categorical–mechanistic extension strives to address this issue, but requires systematic clinical investigation of more precise relationships between psychotropic profiles and discrete mechanisms of action to assess its merits.     

Spread of herpes simplex virus to the cerebrospinal fluid and the meninges in experimental mouse encephalitis

Summary The development of the inflammatory response within the brain, meninges and cerebrospinal fluid (CSF) compartment has been studied for the first time simultaneously in experimental herpes simplex virus (HSV) encephalitis after inoculation via the cornea. Two major viral pathways were found from the eye to the brain: one through the trigeminal nerve to the brain stem and one through the nasolacrimal duct to the olfactory system. Viral antigen was found to be present in the CNS before there were clinical signs or cellular infiltration of brain tissue. Subsequently, the virus spread to all parts of the trigeminal brain stem complex. This phenomenon was accompanied by severe inflammation of the meninges covering the trigeminal root near its entry into the brain stem. The meninges near the entry of the olfactory fila also contained antigen. However, HSV-1 did not spread along meningeal rami of the trigeminal nerve and, consequently, is — at least in this experimental model — not a route to reach the inferior frontal and temporal lobes. The development of CSF changes followed the histopathological development of meningitis and encephalitis closely. HSV-DNA could be detected in the CSF from day 4 post inoculation (p.i.) and HSV-1-specific immunofluorescence in CSF cells was convincingly present on day 5 p.i.; on the same days (4 and 5 p.i.) inflammatory cells were found in apposition to infected cells in the brain. We postulate that HSV is carried to the CSF by infected leukocytes rather than a direct spread to the CSF by simple extension of the encephalitic process to the meningeal surface. Consequently, the chances of detection of viral antigen in CSF cells or HSV-DNA by polymerase chain reaction in CSF at an early, pre-encephalitic stage of disease are slight. The relevance of the findings to the pathogenesis and diagnosis of human herpes simplex encephalitis is discussed.Supported in part by the Stichting Prof. AAH Kassenaar Fonds, Faculty of Medicine, University of Leiden     

Obsessive-Compulsive Disorder in Popular Magazines

To examine what the general public is learning about Obsessive-Compulsive Disorder (OCD) through popular magazines, all articles listed in the Reader's Guide to Periodical Literature under the topic headings of obsessive-compulsive behavior or obsessive-compulsive disorder between 1983 and 1997 were read and rated. Only 31 of the 107 articles under these headings dealt explicitly with OCD, and these were found to be reasonably accurate in their presentations of symptoms, causes, and treatments. Many of the other articles under the target headings, however, focused on incidents of stalking of famous people by obsessed fans. The implications of the content patterns of these articles for understanding and misunderstanding of OCD are discussed.     

Early sterile autopsy in etiological studies on multiple sclerosis

Summary The clinical findings and course in the first 2 cases of multiple sclerosis are described, in whom it was possible to isolate a virus from brain tissue by early sterile autopsy and fusion technique. It is noteworthy that in one of these cases multiple sclerosis probably occurred in female members of the family through three consecutive generations. A report is made on an additional case, in which no virus could be isolated, but in which electron microscopic studies showed two types of virus particles: nucleocapsid-like structures and particles identical in form and size with papova virus. Electron microscopic findings and attempts to cultivate a virus in multiple sclerosis published by other authors are discussed. It is pointed out, that the results described provide as yet no proof for the viral etiology of multiple sclerosis. They support the hypothesis, however, that a virus may play an essential role in the etiology and/or pathogenesis of this disease.Problems in relation to brain biopsy in multiple sclerosis patients are discussed. Early sterile autopsy is considered the most practicable possibility for obtaining tissue material for culturing and for ultrastructural studies in multiple sclerosis.Supported by Deutsche Forschungsgemeinschaft, Schwerpunktprogramm Multiple Sklerose und verwandte Entmarkungskrankheiten.     

“Sporadic” prealbumin-related amyloid polyneuropathy: report of two cases

Summary Two sporadic cases of amyloid polyneuropathy are reported. There was no family history or plasma cell dyscrasia. Both showed sensorimotor and autonomic polyneuropathy with onset in the seventh decade. Amyloid deposits in both cases reacted with anti-human prealbumin sera but not with antisera to human AA and anti-human immunoglobulin light-chain amyloids, including A and A. One patient had the abnormal serum prealbumin and abnormal DNA sequence found in type I familial amyloid polyneuropathy (FAP) (Japanese type). Investigations in sporadic amyloid polyneuropathy should include immunohistochemistry, using antisera to the different amyloid proteins, and the radioimmunoassay and recombinant DNA techniques for diagnosis of FAP.     

Über die sogenannte „zentrale Tonusdifferenz“ mit Nystagmusbereitschaft nach einer Seite

Zusammenfassung An Hand von 71 sowohl otologisch als auch neurologisch-psychiatrisch untersuchten Fällen wird zur Frage der sog. zentralen Tonusdifferenz Stellung genommen.1. In 40% der Beobachtungen waren als Ursache des einseitigen Nystagmusüberwiegens Schäden im Labyrinth bzw. im Bereich des 1. vestibulären Neurons anzunehmen.2. Bei 35% der Untersuchten war sowohl eine periphere als auch zentrale Verursachung möglich. Überwiegend handelt es sich um Patienten mit einem klinischen Halswirbelsäulensyndrom. Der funktionelle Charakter der Störung wird diskutiert.3. In 25% unserer Fälle lagen sicher zentrale Schäden vor, jedoch fand sich mit 2 Ausnahmen kein Anhalt für die Annahme einer Hirnstammläsion als Ursache der Nystagmusbereitschaft nach einer Seite.Therapieversuche werden erwähnt.Der Begriff zentrale Tonusdifferenz wird als mißverständlich abgelehnt und betont, daß dem einseitigen Nystagmusüberwiegen keineswegs ein Hinweischarakter auf eine Hirnstammcontusion zukommt. Die Nystagmusbereitschaft nach einer Seite kann von jedem Abschnitt des vestibulären Systems ausgelöst werden.Teilergebnis eines Forschungsauftrages des Bundesministeriums für Arbeit.     

Potentiation of yawning responses to the dopamine receptor agonists B-HT 920 and SND 919 by pindolol in the rat

Summary Subcutaneous injection of B-HT 920, a dopamine D₂-receptor agonist, in doses ranging from 5 to 100g/kg, induced yawning behavior in rats. Yawning was also elicited by low doses (25–500 g/kg sc) of SND 919, a newly synthesized dopamine receptor agonist. The yawning evoked by B-HT 920 or SND 919 was increased by the -adrenoceptor antagonist pindolol (20mg/kg ip) which alone did not induce yawning. Stereotyped behavior did not appear after B-HT 920 or SND 919 given alone or in combination with pindolol. The results suggest that SND 919 as well as B-HT 920 has stimulatory activity at dopamine D₂-receptors, and that pindolol may exert its enhancement of the yawning response to dopamine receptor agonists via blockade of -adrenoceptors.     

Scanning electron microscopy of malignant gliomas. A comparative study of glioma cells in smear preparations and in tissue culture

Summary Smear preparations from 15 malignant gliomas, 2 metastatic carcinomas and from normal brain were examined by scanning electron microscopy. Tissue culture preparations from malignant gliomas were also studied. In the better differentiated areas of gliomas, the cells in smears were stellate with multiple long interweaving processes 0.25–1.3 m in diameter which could be distinguished from myelinated nerve fibres (1.3–5 m) and from fibrin (0.08–0.3 m) by their thickness and arrangement in the tissue. The relationship of glial processes to blood vessels within the tumour was well demonstrated in smears. Metastatic carcinoma cells lacked the processes seen in glioma cell smears and did not show the same relationship to blood vessels. The more anaplastic glioma cells had fewer processes and ovoid cell bodies covered with surface ruffles and microvilli similar to the cell membrane projections in the nuclear regions of glioma cells in culture. The relationship of the surface morphology of glioma cells in smears to the known invasive nature of these tumours is discussed.     

Myelin lesions in the rabbit eye model as a bystander effect of herpes simplex and visna virus sensitization

Summary Rabbits were immunized with herpes simplex and visna virus in complete Freund's adjuvant. Uv-inactivated herpes virus and the purified visna virus protein p 25 injected intraocularly into these rabbits elicited a moderate inflammatory cell infiltration in the epiretinal myelinated nerve fiber bundles accompanied by signs of demyelination. It is therefore apparent that also viral antigen can induce myelin lesions as a socalled bystander effect of a cell-mediated immune response (bystander demyelination).     

“Echoing approval”: A new speech disorder

We report the cases of two patients presenting a peculiar speech disorder, which we have named echoing approval, in which the patients echo, in replying to questions in a dialogue with short phrases, the positive or negative syntactical construction of a question, or its positive or negative intonation, but without any repetition of whole or part of sentences. When asked about their symptoms, the patients replied 80% of the time with yes, yes, that's right, or exactly to positive questions and no, no or absolutely not to negative questions, regardless of their actual symptoms and oblivious to self-contradiction. In addition, when the examining doctor was speaking to a medical colleague in the patient's presence and using medical terminology that the patient did not understand, he/she agreed or disagreed with any sentence and technical word uttered in a way entirely dependent on the syntax or intonation used. To distinguish this speech disorder from echolalia or verbal perseverations, with which it may be superficially confused, we suggest that it be called echoing approval, as it may be part one of the manifestations of the environment-dependency syndrome. This clinical picture was found to be associated with features of transcortical motor aphasia and frontal lobe signs. One patient had a bilateral callosofrontal malignant glioma and the other a probable multiple system atrophy with global deterioration, pre-eminent frontal release signs, diffuse leukoencephalopathy and multiple lacunes. On the basis of these clinical deficits and neuroimaging features, we are unable to delineate the common, or minimal, lesioned network required for this symptomatology to occur, especially in the absence of a series of patients, and with such a difference in both the location and causes of the lesions. However, bilateral frontosubcortical dysfunction was pre-eminent in the clinical picture in both patients, even though more diffuse brain pathology was seen in one, and it might be speculated that dysfunction of the bilateral orbitofrontal and frontomesial motor frontosubcortical circuits might be involved in the aetiology of this peculiar speech disorder.     

EEG bei hypnotischer Blindheit

Zusammenfassung EEG-Versuche am Menschen wurden durchgeführt mit insgesamt etwa 2500 Augenbelichtungen bei stets geschlossenen Augen. Es wurde experimentiert unter Normal-Bedingungen (Kontrolle) und bei hypnotischer Blindheit.Bei Normal-Bedingung (ohne Hypnose) ergab die Lichtreizung eine signifikante Amplituden- und Frequenzminderung des-Rhythmus gegenüber der Zeit unmittelbar vor der Lichtreizung. Genauso verhielt es sich in Hypnose ohne Suggestion von Blindheit. Während hypnotischer Blindheit dagegen zeigte sich eine signifikante Vergröerung der Amplitude unter Lichtreiz und keine signifikante Veränderung der Frequenz. Versager bei hypnotischer Blindheit, die trotz Blindsuggestion Licht sahen, wiesen Amplituden- und Frequenzminderung auf so wie im Mittel alle Versuche unter Normal-Bedingungen (ohne Hypnose).Die Latenzzeit der Amplitudenminderung nach Lichtreizung (onLatenz) war im Mittel um die Hälfte kürzer als die Amplitudenerhöhung. Occipital war gegenüber frontal die on-Latenz der Amplitudenminderung kürzer, frontal aber hatte die Amplitudenerhöhung die kürzere Latenz.Die Amplitudenerhöhung unter Lichtreiz bei hypnotischer Blindheit wird als Ausdruck einer Hemmung der Perception gedeutet.     

Sporadic cerebral amyloid angiopathy: pathology, clinical implications, and possible pathomechanisms

Cerebral amyloid angiopathy (CAA) was observed for the first time nearly 100 years ago and systematically described in 1938. It is a common finding in elderly individuals, defined by -amyloid peptide (A) depositions in cerebral blood vessels, and associated with Alzheimers disease (AD). A variety of genetic mutations cause hereditary forms of CAA; in this review, however, only the sporadic variant of CAA is considered. In CAA, A depositions primarily occur in the abluminal portion of the tunica media, and with increasing severity all layers of the blood vessel wall are infiltrated and an additional spread of A into the surrounding neuropil may be seen (i.e., dyshoric changes). CAA is most pronounced in the occipital lobe and its distribution is usually patchy. The relationship between CAA and AD is poorly understood; however, low positive correlations between the severity of both CAA and AD pathology have been observed. CAA is a frequent cause of (warfarin-associated) intracerebral hemorrhage, and the diagnosis of probable CAA-related hemorrhage can be made during life with high accuracy. Both APOE-4 and APOE-2 are risk factors for CAA, while only APOE-2 increases the risk for hemorrhage in CAA. Although the role of CAA as an independent risk factor for cognitive decline is unclear, severe CAA is likely to lower the threshold for clinically overt dementia in neurodegenerative diseases. As for the origin of A in CAA, it may be both produced by smooth muscle cells (vessel wall) and derived from neurons in the course of perivascular drainage.     

Selective vulnerability in the gerbil hippocampus: Morphological changes after 5-min ischemia and long survival times

Summary The morphology of the hippocampus of Mongolian gerbils was investigated by light and electron microscopy after 5-min forebrain ischemia and survival times of up to 10 months. After 3 weeks recirculation only 5.8% of pyramidal neurons of the CA1 (cornu ammonis 1) sector had survived but the thickness of the inner and outer hippocampal layers did not change. After recirculation times of 6 and 10 months the number of surviving neurons declined no further but all layers of the CA1 subfield shrank markedly. Ultrastructurally, many but not all surviving CA1 neurons were altered. After 3 weeks both dark and pale type neurons were present, while after 6 and 10 months only the pale type of injury persisted. Axonal enlargements and myelin breakdown were observed at all survival times up to 10 months of recirculation. The astrocytes of CA1 sector contained numerous glial fibrils which were most pronounced after the longer recirculation times. The stratum radiatum presented intact presynaptic terminals densely packed with an abundance of clear vesicles even after survival of 10 months. Initially, morphologically damaged postsynaptic structures were still attached to these terminals but they disappeared after longer recirculation times. However, even after 10 months some intact synapses were observed involving dendrites which probably originated from surviving CA1 neurons. In CA3 sector and dentate gyrus no ultrastructural changes occurred at any survival time. The close association of surviving CA1 neurons with intact presynaptic terminals and reactive glial cells may be of importance for the development of epileptogenic foci which are characteristic of this particular brain region.     

Die spektralphotometrische Analyse des Liquor cerebrospinalis im UV-Licht

Zusammenfassung Die spektralphotometrische Bestimmung der Absorptionskurve des natürlichen Liquors im UV-Licht gestattet in exakt reproduzierbarer Weise normale und pathologische Liquores zu unterscheiden. Dies ist namentlich bei Verlaufskontrollen von Bedeutung. Ein konstantes Absorptionsmaximum (A) findet sich im kurzwelligen Bereich bis 240 m und ist zur quantitativen Eiweißbestimmung mit einer für die klinischen Bedürfnisse hinreichenden Genauigkeit geeignet. Eine von den quantitativen Eiweißwerten unabhängige Absorptionsbande ( A) hat ihr Maximum bei allen normalen und den meisten pathologischen Liquors bei 266 m Eine Verschiebung nach 275 m kommt vereinzelt bei pathologischen Liquores vor.Eine starke A mit einem Durchlaßgrad von weniger als 30% spricht auch bei im übrigen normalen Liquorwerten für pathologische Veränderungen.Das mittels Perchlorsäure gefällte Liquoreiweiß zeigt in alkalischer Lösung ein dem Grade nach von dem Eiweißgehalt abhängiges Absorptionsmaximum bei 215 m und eine flache Absorptionsbande zwischen 275–285 m.     

Liquorkomplement und Multiple Sklerose

Zusammenfassung 1. In 239 Liquores, darunter 47 MS-Fälle und 91 normale Kontrollen, wurden Komplement und Komplementfaktoren (C₁, C₂, C₃ und C₄) bestimmt.2. Im normalen Liquor ist in der Regel keine Gesamtkomplementaktivität vorhanden. Dagegen ist die C₁- wie C₄-Aktivität praktisch immer und C₂-sowie C₃-Aktivität in über der Hälfte der Fälle zu finden. Das Komplementmuster im Liquor ist daher im Gegensatz zum Serum unvollständig.3. Bei erhöhtem Eiweiß zeigt der Liquor dagegen häufig Gesamtkomplementaktivität. Je höher das Liquoreiweiß ist, um so höher ist der Gehalt an C₂, C₃ und Gesamtkomplement. Diese Beziehungen zwischen Gesamteiweiß und Komplementaktivität gelten für normalen wie pathologischen Liquor einschließlich der MS-Fälle.4. Im MS-Liquor sind C₂, C₃ und Gesamtkomplement seltener zu finden als bei den Kontrollen. Bei den MS-Patienten ist C₂ und C₃ im akuten Schub herabgesetzt. C₃ nimmt im Verlauf der Erkrankung wahrscheinlich ab.5. Mit Antikomplementserum wurde _1C-Globulin, ein Teilfaktor von C₃, im Liquor von 55 MS-Patienten und 42 Kontrollen bestimmt. Es besteht kein Unterschied zwischen MS und Kontrolliquor. Auch bei akut entzündlicher MS ist _1C nicht vermindert.6. In der Diskussion wird auf widersprechende eigene Befunde über _1C-Inaktivierung im Serum während der akut entzündlichen MS-Phase hingewiesen.

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Summary 1. Complement and complement factors (C₁, C₂, C₃ and C₄) were determined in 239 specimes of cerebrospinal fluid (CSF) including 47 cases of Multiple Sclerosis (MS) and 91 normal controls.2. In general, total complement activity is absent in normal specimens while that of C₁ and C₄ can be found practically always and that of C₂ and C₃ in more than half of the cases. Therefore, the pattern of complements in the CSF is incomplete as opposed to that of serum.3. In contrast, samples with increased protein content frequently yield total complement activity. The higher the protein content of CSF the higher the content of C₂, C₃ and total complement. This relationship between amount of total protein and complement activity applies both to normal and pathological CSF specimens including those from MS.4. In cerebrospinal fluid from patients with MS, C₂, C₃ and total complement are found less frequently than in that from controls. C₂ and C₃ are diminished in patients with an acute exacerbation of MS. C₃ decreases probably in the course of the disease.5. _1C-globulin, a component of C₃, was determined with anticomplement sera in specimens from 55 patients with MS and from 42 controls. There is no difference between CSF of MS and controls. Even in acutely inflammatory cases of MS, _1C is not diminished.6. Discussing his results the author points out discrepancies concerning the nactivation of _1C in serum during acutely inflammatory episodes of MS.

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Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

Amyloid β peptide 1–42 highly correlates with capillary cerebral amyloid angiopathy and Alzheimer disease pathology

Recent studies reported both positive [Thal et al. (2003) J Neuropathol Exp Neurol 62:1287–1301] and negative [Tian et al. (2003) Neurosci Lett 352:137–140] correlations between cerebral amyloid angiopathy (CAA) and Alzheimers disease (AD) pathology. We have recently shown high correlations between neuritic AD pathology and amyloid peptide (A) deposits in the capillary/pericapillary compartment (CapCAA) with only low correlations to general CAA (non-capillary). We have now studied the relationship between CapCAA and AD pathology with respect to the distribution of A40 and 42 in the frontal cortex of 100 human postmortem brains from both male and female, demented and non-demented patients (mean age ± SD 84.3±9.3 years). Using polyclonal antibodies to A40 and 42, capillary and plaques positivity were assessed semiquantiatively on a four-point scale. A42 deposits in capillaries correlated highly with both A42 deposits in plaques and morphological AD criteria (CERAD, Braak stages, and NIA-Reagan-Institute criteria), while only a low correlation with CAA was observed. A40 deposits in capillaries differed morphologically from A42 ones: they were limited to capillary walls, were significantly less frequent in both capillaries and plaques compared to A42 (P<0.01), and showed a low correlation with morphological AD criteria (P<0.05) and general CAA (P<0.01). By contrast, A42 deposits were seen in the glia limitans rather than in capillary walls themselves, and showed high correlation with morphological AD criteria (P<0.01). These data indicate that CapCAA is characterized by A42 deposits in pericapillary spaces or in the glia limitans. A low correlation between CAA and CapCAA, but high correlations between morphological AD criteria and CapCAA suggest different pathomechanisms for both types of CAA, and a close relation between CapCAA and AD pathology (both neuritic and plaque type). These data support the concept of a neuronal origin of A via drainage from interstitial fluid from the central nervous system along basement membranes to capillaries.List of Abbreviations AD Alzheimer disease - A beta amyloid peptide - A 40/42 CapS score of deposits of A 1–40/42 in capillaries - A 40/42 C number of A 1–40/42 positive cortical vessels - A 40/42 PS score of deposits of A 1–40/42 in plaques - A 40/42 TS total score of A 1–40/42 deposits - A 40/42 Csev severity of A 1–40/42 affection of cortical vessels - A 40/42 CS A 1–40/42 cortical score - A 40/42 L percentage of A 40/42 positive leptomeningeal vessels - A 40/42 Lsev severity of A 40/42 affection of leptomeningeal vessels - A 40/42 LS A 40/42 leptomeningeal score - ACTS A cortical total score - ALTS A leptomeningeal total score - CAA cerebral amyloid angiopathy - CAATS CAA total score - CapCAA capillary CAA - CERAD Consortium to Establish a Registry of Alzheimers Disease - NFT neurofibrillary tangle - NIA National Institute of Aging - NIA-RI National Institute of Aging and Reagan Institute - NP neuritic plaque - SP senile plaque - TS total scoreAn erratum to this article can be found at