Neurotensin immunoreactivity in post-mortem brain is increased in Down's syndrome but not in Alzheimer-type dementia

Neurotensin immunoreactivity and choline acetyltransferase (ChAT) activity were measured in post-mortem brain from 10 cases of Down's syndrome (7 aged 53-63 years, one aged 27 years, one aged 16 months and one aged 10 months), 6 cases of Alzheimer-type dementia (ATD) and 19 control subjects (13 aged 40-88 years and 6 aged 9-18 months). Neurotensin concentrations in anterior and basal hypothalamus, amygdala, septal area, caudate nucleus and temporal cortex were unaltered in ATD. The concentrations of neurotensin were significantly increased in the caudate nucleus, temporal cortex and frontal cortex in the cases of Down's syndrome aged 53-63 years with the neuropathological features of ATD, and were also increased in the cerebral cortex of the 27-year-old, which did not have the neuropathological features of ATD, and in two infant Down's cases. ChAT activity was reduced in the ATD and the 53-63-year-old cases of Down's syndrome, but not in the 27-year or 10-month-old Down's cases. The increased neurotensin concentrations appear to be a feature of Down's syndrome not related to the presence of plaques and neurofibrillary tangles or to a deficit in ChAT activity.     

Cerebrospinal fluid monoaminergic metabolites are elevated in adults with Down's syndrome

Under conditions of rest and a low monoamine diet, brain monoamine activity was examined in young (less than 35 years) and old (greater than 35 years) adults with Down's syndrome and in control subjects by measuring the cerebrospinal fluid (CSF) and plasma concentrations of the neurotransmitter norepinephrine, and of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy 4-hydroxyphenylglycol (MHPG), the respective metabolites of the neurotransmitters serotonin, dopamine, and norepinephrine. There were no age-related differences in metabolite concentrations in either the Down's syndrome or control subjects. CSF concentrations of 5-HIAA, HVA, and norepinephrine were significantly higher in young subjects with Down's syndrome as compared with young controls, and CSF concentrations of 5-HIAA and norepinephrine were significantly higher, by twofold or more, in old subjects with Down's syndrome as compared with older controls. The results suggest that monoamine turnover and brain functional activity involving monoamines is elevated in Down's syndrome, and that the early neuropathological changes in the disorder are not associated with a monoamine deficit.     

Effect of neonatal nociceptin or nocistatin imprinting on the brain concentration of biogenic amines and their metabolites

Noradrenaline (NA), dopamine (DA), homovanillic acid (HA), serotonin (5HT) and 5-hydroxyindole acetic acid (5HIAA) content of five brain regions (hypothalamus, hippocampus, brainstem, striatum and frontal cortex) and the cerebrospinal fluid (CSF) was measured in adult (three months old) male and female rats treated neonatally with a single dose of 10 microg nociceptin (NC) or 10 microg nocistatin (NS) for hormonal imprinting. The biogenic amine and metabolite content of cerebrospinal fluid was also determined. In NC treated animals the serotonergic, dopaminergic as well as noradrenergic systems were influenced by the imprinting. The 5HT level increased in hypothalamus, the 5HIAA tissue levels were found increased in hypothalamus. Hippocampus and striatum and the HVA levels increased highly significantly in brainstem. Dopamine level decreased significantly in striatum, however in frontal cortex both noradrenalin and 5HIAA level decreased. Nevertheless, in NS-treated rats decreased NA tissue levels were found in hypothalamus, brainstem and frontal cortex. Decreased DA levels were found in the hypothalamus, brainstem and striatum. NS imprinting resulted in decreased HVA level, but increased one in the brainstem. The 5HT levels decreased in the hypothalamus, brainstem, striatum and frontal cortex, while 5HIAA content of CSF, and frontal cortex decreased, and that of hypothalamus, hippocampus and striatum increased. There was no significant difference between genders except in the 5HT tissue levels of NC treated rats. Data presented show that neonatal imprinting both by NC and NS have long-lasting and brain area specific effects. In earlier experiments endorphin imprinting also influenced the serotonergic system suggesting that during labour release of pain-related substances may durably affect the serotonergic (dopaminergic, adrenergic) system which can impress the animals' later behavior.     

Reductions in soluble brain proteins in older subjects with Down's syndrome

Soluble proteins from temporal cortex and caudate nucleus from 6 cases of Down's syndrome (5 aged over 50 and 1 aged 27 years) and 7 controls were analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. In older Down's syndrome cases, reductions in tubulin and 5 other proteins were observed in cortex which had the neuropathology of Alzheimer's disease but not in caudate nucleus. No protein changes or neuropathological features of Alzheimer's disease were found in the youngest Down's syndrome case. The protein changes appear to be associated with the neuropathological features of Alzheimer's disease and not with Down's syndrome itself.     

Brain monoamines in cases with Down's syndrome with and without dementia

Summary Three cases of Down's syndrome, one of which had a clinical history of a presenile dementia during final years, were analyzed for the content of tyrosine (Tyr), dopamine (DA), noradrenaline (NA), tryptophan (Try), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in the following regions: the caudate nucleus, the putamen, the thalamus, the mesencephalon, and the hippocampus. A rather generalized reduction of DA, NA, 5-HT, and 5-HIAA was noted in the demented DS case.     

Comparative coherence studies in healthy volunteers and Down's syndrome patients from childhood to adult age.

Within the scope of the Munich Pediatric Longitudinal Study, EEG coherence was studied in 212 Down's syndrome patients and 342 healthy controls aged from 6 months up to 30 years. The digitalized EEG records were subjected to spectral analysis. Frequency band-related coherences were calculated to reveal age-specific differences in the functional relationship between two brain areas in Down's syndrome patients and controls. The results show that in the "eyes-open" state the intra-hemispheric coherence in the alpha band was significantly lower (P less than 0.05) in the Down's syndrome patients than in the controls whereas that in the delta bands it was generally higher. The intra-hemispheric coherence in the "eyes-closed" state was generally higher in the Down's syndrome groups than in the controls; however, significant differences could be detected only in some age groups. The age-specific development of coherence in the inter-hemispheric parieto-occipital region was almost identical in Down's syndrome children as in controls, both with open and closed eyes. The most distinct differences were found in the fronto-central inter-hemispheric coherence (P less than 0.01), while the coherence deficiencies in the Down's syndrome group became more prominent with increasing age from school age onwards. These electrophysiological results are compared with the results of neuropathological and neurophysiological studies of other authors. It can be suggested that there are correlations with a significantly small number of dendritic spines in Down's syndrome patients, which was determined in neuropathological examinations. A neuronal model of interpretation is presented which explains the increasing developmental deficit with age in Down's syndrome children.     

Effect of chronic nicotine administration on monoamine and monoamine metabolite concentrations in rat brain

The effects on rat brain tissue monoamine and monoamine metabolite concentrations of chronic nicotine administration at two doses (3 and 12 mg/kg/day) using constant infusion were studied. After 21 days of treatment, tissue concentrations of dopamine (DA), norepinephrine (NE), 5-hydroxytryptamine (5-HT), and several metabolites in striatum, hypothalamus, and frontal cortex were determined by high performance liquid chromatography with electrochemical detection. Compared with a control group, nicotine treatment significantly decreased NE in frontal cortex but not in other regions. The concentration of 5HT also was decreased in frontal cortex but increased in the hypothalamus at the higher dose of nicotine. The 5HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) was not significantly altered in any region. The 5HT index (5-HIAA/5-HT) was significantly decreased in the hypothalamus and increased in frontal cortex at the higher dose. Concentrations of DA and the metabolite homovanillic acid (HVA) were not significantly altered by nicotine. Nevertheless, significant decreases in the DA metabolite dihydroxyphenyl-acetic acid (DOPAC) were observed in both striatum and hypothalamus. Moreover, the DA index [(DOPAC + HVA)/DA] was significantly decreased in all three brain regions. In contrast to other studies using acute dose and in vitro perfusion paradigms that have reported increased CNS catecholamine release stimulated by nicotine, chronic administration appears to be associated with decreased catecholamine turnover in some brain regions.     

Use of electroencephalography to detect Alzheimer's disease in Down's syndrome

We studied the role of electroencephalography (EEG) in the diagnosis of Alzheimer-type dementia in patients with Down's syndrome. 197 patients with Down's syndrome were monitored for 5 to 8 years. Aspects of cognitive functioning were assessed twice yearly. EEGs were scored in a blind fashion, and changes in the EEG were compared to changes in cognitive functioning. When possible, a neuropathological post-mortem examination was performed. Cognitive functioning was drastically reduced in 29 patients. The dominant occipital rhythm became slower at the onset of the cognitive deterioration, and eventually disappeared. In 11 of these patients neuropathological examination showed a severe form of Alzheimer's disease. Changes in the frequency of the dominant occipital rhythm could distinguish between Alzheimer's disease or other causes as underlying the cognitive decline. Slowing of the dominant occipital rhythm seems to be related to Alzheimer's disease in patients with Down's syndrome, and the frequency of the dominant occipital activity decreases at the onset of cognitive deterioration. The EEG is thus an important tool in the clinical diagnosis of Alzheimer-type dementia in patients with Down's syndrome.     

Regional monoamine and metabolite levels in a feline brain tumor model

The presence of a brain tumor alters regional cerebral blood flow, oxygen consumption, and glucose utilization in adjacent and remote brain tissue, but its effect on brain neurotransmitter levels is unclear. In the present report, the levels of noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT), 3,4-dihydroxyphenyl-acetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindole-acetic acid (5-HIAA) in tumor tissue and gray and white matter obtained from cats with induced brain tumors were measured. Glioma cells (9L) were xenotransplanted into the central white matter of the right hemisphere, and 15 d later the brains were frozen in vivo. Samples of tumor, parietal (peritumor), temporal, and frontal gray and white matter were divided for analysis of water content and quantification of amines and their metabolites. The water content of white matter, but not gray matter, adjacent to the tumor was increased. Neurotransmitter amine and metabolite levels were much lower in the tumor than in brain tissue. In gray matter adjacent to the tumor, concentrations of DA and its metabolites HVA and DOPAC were significantly decreased from control, whereas 5-HIAA was increased. The NA, DA, HVA, and DOPAC levels were decreased in temporal gray matter, whereas all amine and metabolite levels were unchanged in frontal gray matter. These results indicate that altered neurotransmitter metabolism is one of the effects of the presence of a brain tumor.     

Down's syndrome: intellectual and behavioural functioning during adulthood

ABSTRACT. Previous cross–sectional studies of Down's syndrome have suggested thatdeficits in cognitive and neurological functioning after the age of 35 years are symptomatic of Alzheimer's disease. It has been claimed that this pattern corresponds to post-mortem neuropathological findings of Alzheimer's disease in all Down's syndrome patients who die aged over 35 years. In the present study of Down's syndrome patients aged between 19 and 49 years, results showed that, for those over 35 years, intellectual deterioration had occurred in less than a third. No relationship was found between chronological age and the level of self care skills or the presence of disturbed behaviour. Results are discussed in terms of the interpretation of the existing neuropathological literature, the methodology of future studies and clinicaldecisions regarding hospitalized patients with Down's syndrome.     

Cholinergic enzymes in the spinal cord in Alzheimer-type dementia

Summary Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) were measured in anterior and posterior grey matter of the lumbar spinal cord and in temporal and frontal cortex from six cases of Alzheimer-type dementia (ATD), one case of Down's syndrome, three cases of schizophrenia (SZ) and six controls. Compared with control and SZ values, ChAT and AChE were reduced in ATD cerebral cortex. ChAT was reduced, and AChE unaltered, in ATD spinal cord. Decreased cord ChAT may be related to electrophysiological abnormalities which have been reported in motor nerves of patients with Alzheimer's disease.     

Overexpression of s100beta in Down's syndrome: correlation with patient age and with beta-amyloid deposition

S100beta is an astrocyte-derived uritotrophic' cytokine which has been implicated in the pathogenesis of Alzheimer's disease. S100beta overexpression by plaque-associated astrocytes correlates with growth of abnormal (strophic') neurites in beta-amyloid plaques, one of the major neuropathological hallmarks of Alzheimer's disease. As the characteristic neuropathological changes of Alzheimer's disease are virtually universal in middle-aged Down's syndrome patients, studies of Down's syndrome patients provide a unique opportunity to investigate the pathophysiological processes underlying the development of Alzheimer-type neuropathological changes. Computerized morphometric analysis was used to quantify astrocyte activation and astrocytic expression of S100beta, and to correlate these with beta-amyloid deposition, in a clinically well-characterized cohort of Down's syndrome subjects, aged 13-65 years. There were significant positive correlations between S100beta expression and patient age, and between S100beta expression and cerebral cortical beta-amyloid deposition. Moreover, the numbers of activated (enlarged) astrocytes overexpressing S100beta showed a significant correlation with the numeric density of beta-amyloid plaques, from the youngest to the oldest ages and within age ranges where pathology is most florid, while no such relationship was found between the numbers of small, non-activated S100beta-immunoreactive cells and numerical density of beta-amyloid plaques. These correlations, together with established functions of S100beta, are consistent with the idea that S100beta overexpression promotes beta-amyloid plaque formation and progression in Down's syndrome.     

Effects of an oral glucose load on plasma neurotransmitters in humans: involvement of REM sleep?

Plasma noradrenaline (NA), adrenaline (Ad), dopamine (DA), platelet serotonin (p5HT), free serotonin (f5HT), glucose, heart rate (HR) and blood pressure (BP) were measured before and after an oral load of glucose (OGTT) in 100 normal humans. One sham-feeding test was performed in every subject 2-3 weeks before OGTT. Aside from glucose rise, significant increases in NA, p5HT and the NA/Ad ratio were registered. No significant changes were observed in Ad, DA, f5HT, HR and BP mean +/- SE values. Significant reductions in the NA/p5HT, Ad/p5HT and DA/p5HT ratios' mean values were registered at 90 and 180 min. Several significant correlations were found amongst plasma neurotransmitters. Very high positive correlations were obtained when NA, Ad and DA were plotted against the ratio of each one of them over p5HT; however, they (r = 0.99) decreased significantly at 90 and 180 min. Upon evaluation of these results we infer that quiescence of adrenal glands occurs during OGTT. Under such circumstances, plasma neurotransmitters are left under the control of a central bipolar system: noradrenergic-parasympathetic. All numerical data strongly suggest that the noradrenergic system predominates at 60, 120 and 210 min, whereas parasympathetic predominance occurs at 90 and 180 min. The fact that the latter is interfered by atropine reinforces this hypothesis. Analyses of correlations also suggest that DA and p5HT probably act as a buffer and modulate the excessive increase in NA plasma levels registered during OGTT.     

Acetylcholine and aromatic amine systems in postmortem brain of an infant with Down''s syndrome

Adult cases of Down's syndrome often show histologic and biochemical changes comparable to those seen in severe Alzheimer's disease, but it is not known whether these are congenital or acquired defects. Cell counts of the basal forebrain cholinergic system innervating the cortex in a 5.5-month-old male infant with Down's indicated about 50% of the number of cells expected at birth but this is in the range of cell numbers found in healthy middle-aged normals. The noradrenergic system of the locus ceruleus has the expected complement of cells for normal newborns. The activities of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), glutamate decarboxylase, and tyrosine hydroxylase in a number of brain regions are reported for this infant, two cases of crib death, and a group of normal adults. The regional distributions of the enzymes in the infants were generally as expected from adult control data except for that of ChAT in one of the two cases of crib death; the AChE activities seemed extraordinarily high, especially in the case of Down's syndrome. Data on the concentrations of the catecholamines, serotonin, and their metabolites are also given but, like the enzyme data, are difficult to interpret in the absence of controls for the neonatal period.     

Alzheimer's disease. Aminergic-cholinergic alterations in hypothalamus

To better understand the role of the hypothalamus in Alzheimer's disease (AD), we have measured dopamine, norepinephrine (NE), and serotonin (5HT) levels, tritiated spiperone and tritiated serotonin blinding, and choline acetyltransferase (ChAT) and acetylcholinesterase activity in seven subregions of the hypothalamus from 18 normal control subjects and ten patients with AD. We have found a significant reduction of 5HT in the anterior hypothalamus, lateral hypothalamus, and posterior lateral hypothalamus and a decline in spiperone binding in the anterior hypothalamus of patients with AD. The ChAT activity was found to be diminished only in the posterior lateral hypothalamus of patients with AD. No NE or dopamine alterations were found in any region of the AD hypothalamus. In the normal hypothalamus, dopamine, NE, and 5HT were found to be regionally distributed. Our study documents region-specific neurotransmitter abnormalities in the AD hypothalamus and raises the question of the relationship of these changes, especially in 5HT, to some of the noncognitive clinical alterations observed in AD.     

Neurochemical, neuroautonomic and neuropharmacological acute effects of sibutramine in healthy subjects

Sibutramine is a neuropharmacological drug that exerts central (CNS) and peripheral effects including noradrenaline (NA), and serotonin (5-HT) uptake inhibition. In addition, the drug is able to induce release from DA axons. We measured levels of circulating neurotransmitters in 20 healthy subjects during supine-resting (fasting) state before and after 15 mg of oral sibutramine. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were also monitored. Sibutramine triggered sustained and progressive increase of NA, NA/Ad ratio and DBP. Slight increases of DA were also registered between the 60 and 240 min periods. The rise in DA tended to fade progressively, reaching basal level at 360 min period. Diastolic blood pressure, but neither SBP nor HR, showed significant increases that correlated positively with NA/Ad ratios. Slight but significant negative correlation was also found between DBP and DA. This correlation tended to fade throughout the trial to show no significance at the 360 min period. Although neither plasma serotonin (f-5HT) nor platelet serotonin (p-5HT) values showed significant variation throughout the trial, the f-5HT/p-5HT ratio showed significant decrease throughout. Significant negative correlation was found between f-5HT/p-5HT ratio and NA/Ad ratio. Our results indicate that sibutramine stimulates neural sympathetic activity but not adrenal sympathetic activity in healthy individuals. Further, sibutramine lowers parasympathetic activity. The moderate rise in diastolic blood pressure triggered by sibutramine would be associated with CNS-NA enhancement plus parasympathetic inhibition.     

Serological alpha 1-antichymotrypsin in Down's syndrome and Alzheimer's disease.

alpha 1-Antichymotrypsin (ACT) is a serine protease inhibitor that is markedly elevated in the serum and cerebrospinal fluid of patients with Alzheimer's disease (AD). Patients with Down's syndrome are known to develop neuropathological changes of AD by age 40 years and many become demented. Therefore, in the present study, we obtained serum ACT levels from patients with Down's syndrome and AD, diagnosed by autopsy or clinically, and healthy control subjects. Newman-Keuls' multiple range test revealed a significantly greater (p less than 0.01) mean ACT level in the Autopsy AD (906.4 +/- 94.64 mg/L) and Clinical AD (745.00 +/- 59.95 mg/L) groups in contrast to the Old Control group (531.00 +/- 23.05 mg/L). The mean ACT level of the Down's Syndrome group (513.33 +/- 14.73 mg/L) was not significantly different from that of the Young Control subjects. Furthermore, we did not observe a positive correlation of ACT levels with age in the Down's Syndrome group, in spite of the age-dependent premature increase in neuropathological changes of AD that are known to occur in patients with Down's syndrome. A positive correlation between serum ACT levels and the density of plaques or tangles, neuropathological hallmarks of AD, in brains of patients with AD also did not exist. Thus, our results suggest that ACT levels may not parallel the development of the classical neuropathological hallmarks of AD.     

Monoaminergic and cholinergic synaptic markers in the nucleus basalis of Meynert (nbM): normal age-related changes and the effect of heart disease and Alzheimer's disease.

Neurotransmitter markers for acetylcholine, serotonin (5-HT), and dopamine (DA) were measured in autopsied human nucleus basalis of Meynert (nbM) from nondemented individuals without heart disease (non-HD) (age range, 4-84 years; n = 77), nondemented individuals with heart disease (HD) (age range, 57-92 years; n = 23), and individuals with Alzheimer's disease (AD) (age range, 59-92 years; n = 22). No significant differences in any chemical marker were found between age-matched HD and non-HD individuals. The activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), and [3H]spiperone binding were regionally distributed within the nbM in control (non-HD) subjects less than 54 years of age. The activity of AChE, 5-[3H]HT binding, and the content of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 5-HT were regionally distributed in the nbM in non-HD, HD, and AD subjects more than 54 years of age. The binding of [3H]spiperone was regionally distributed in the nbM in HD and AD subjects more than 54 years of age, only. Activity of ChAT and AChE, content of 5-HT, 5-HIAA, and DA, binding of 5-[3H]HT, and the turnover number for DA (ratio of HVA/DA) all decreased with increasing age in the non-HD control population. The content of HVA, binding of [3H]spiperone, and the turnover number for 5-HT (ratio of 5-HIAA/5-HT) did not change with increasing age. Significant reductions in ChAT and AChE activities were found in AD nbM compared with postmortem interval- and age-matched HD and non-HD individuals. The reduction of 5-HT and 5-HIAA content and [3H]spiperone binding in individuals with AD of all ages suggests a loss of functional serotonergic innervation of the nbM. Dopaminergic synaptic markers were less affected in AD nbM, although turnover numbers for both DA and 5-HT were increased in AD. Receptor upregulation in response to presynaptic deficits did not occur for DA or 5-HT.     

Agonist-evoked Ca2+ transients in primary astroglial cultures--modulatory effects of valproic acid.

Cytosolic Ca2+ ([Ca2+]i) activity was measured in individual type 1 astroglial cells in primary culture after exposure to glutamate (Glu), quisqualate (QA), gamma-aminobutyric acid (GABA), 5-hydroxytryptamine (5HT), and noradrenaline (NA) by using the Ca2+ indicator dye fura-2/AM in a computerized microspectrofluorimetric system. Various patterns of Ca2+ transients were observed, but the most common was biphasic, having an initial sharp peak, rising immediately after stimulation, and then declining to a lower but sustained Ca2+ level. The only substance that diverged from this pattern was GABA, which induced a Ca2+ response with longer latency and a single-phase curve. The effects of the anticonvulsive drug Na(+)-valproate (VPA) were also investigated. After both acute and chronic (5-7 days) exposure to 10(-4) M VPA, the GABA-evoked rises in [Ca2+]i were completely inhibited. VPA also had acute effects on the 5HT- and Glu-evoked Ca2+ spikes. The Ca2+ responses after 5HT stimulation were greatly reduced after exposure to 10(-4) M VPA. The responses after glutamate stimulation were, on the contrary, increased after a similar exposure. No VPA effects were seen on the curve patterns of QA and NA stimulations. The most frequent agonist-evoked responses were seen after stimulation with 5HT and NA, where over 80% of the tested cells responded. For QA and Glu, the response frequencies were about 40% each, while for GABA it was 20%. The responses after 5HT and NA stimulation were blocked to baseline levels after exposure to ketanserin (5HT2 receptor antagonist) and a combination of prazosin, yohimbine, and propranolol (alpha 1, alpha 2, and beta adrenoceptor antagonists, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuroanatomy of Down's syndrome: a high-resolution MRI study

OBJECTIVE: Down's syndrome, the most common genetic cause of mental retardation, results in characteristic physical and neuropsychological findings, including mental retardation and deficits in language and memory. This study was undertaken to confirm previously reported abnormalities of regional brain volumes in Down's syndrome by using high-resolution magnetic resonance imaging (MRI), determine whether these volumetric abnormalities are present from childhood, and consider the relationship between neuroanatomic abnormalities and the cognitive profile of Down's syndrome. METHOD: Sixteen children and young adults with Down's syndrome (age range=5-23 years) were matched for age and gender with 15 normal comparison subjects. High-resolution MRI scans were quantitatively analyzed for measures of overall and regional brain volumes and by tissue composition. RESULTS: Consistent with prior imaging studies, subjects with Down's syndrome had smaller overall brain volumes, with disproportionately smaller cerebellar volumes and relatively larger subcortical gray matter volumes. Also noted was relative preservation of parietal lobe gray and temporal lobe white matter in subjects with Down's syndrome versus comparison subjects. No abnormalities in pattern of brain asymmetry were noted in Down's syndrome subjects. CONCLUSIONS: The results largely confirm findings of previous studies with respect to overall patterns of brain volumes in Down's syndrome and also provide new evidence for abnormal volumes of specific regional tissue components. The presence of these abnormalities from an early age suggests that fetal or early postnatal developmental differences may underlie the observed pattern of neuroanatomic abnormalities and contribute to the specific cognitive and developmental deficits seen in individuals with Down's syndrome.