Variability in blood-based amyloid-beta assays: the need for consensus on pre-analytical processing

The objective of this study was to examine the diagnostic accuracy of imaging and CSF biomarkers in clinically ambiguous dementia (CAD). 69 patients were prospectively followed. The endpoint was clinical diagnosis at follow-up of 24 months based upon existing criteria. Medial temporal lobe atrophy score on MRI, distinctive patterns on 99 mTc-HMPAO-SPECT, and CSF levels of amyloid-β peptide, total tau protein, and P-tau181P were used together with neuropsychological testing to assess Se (sensitivity) and Sp (specificity) of separate and combined markers. 60 patients reached the endpoint. A definite diagnosis was achieved in 48 patients. CSF biomarkers had a Sp of 71% and a Se of 100% for Alzheimer's disease (AD) diagnosis. Sp increased to 88% and 93% when MRI and MRI + SPECT were combined, at the expense of Se. CSF biomarkers levels also provided clues to frontotemporal (FTD) or vascular dementias (VaD) diagnosis when situated in an intermediate range between normal and pathological values. MRI and SPECT contributed mostly to the diagnosis of VaD (Se 88%, Sp 75%) and FTD (Se 73%, Sp 78%), respectively. Initial neuropsychological testing had a poor diagnostic accuracy, except for a neuropsychiatric inventory score >40 for the diagnosis of FTD (Se 73%, Sp 84%). Independent of the clinical diagnosis, medial temporal lobe atrophy and total-tau were best correlated with cognitive decline at 2 years. In conclusion, CSF biomarkers efficiently predict evolution toward an AD phenotype in CAD. Imaging biomarkers mostly contribute to the differential diagnosis between non-AD dementias. Initial neuropsychological testing was poorly contributive in CAD diagnosis.     

Cerebrospinal fluid tau, phospho-tau181 and β-amyloid1−42 in idiopathic normal pressure hydrocephalus: a discrimination from Alzheimer's disease

The aim of the present study was the quantitation of total tau protein ( τ _T), tau phosphorylated at threonine 181 ( τ _P-181) and β -amyloid₁₋₄₂ (A β 42) in the cerebrospinal fluid (CSF) of patients with idiopathic normal pressure hydrocephalus (iNPH), Alzheimer's disease (AD) and controls. Double sandwich ELISAs (Innogenetics) were used for the measurements. Total tau was significantly increased in iNPH and highly increased in AD as compared with the control group, whilst A β 42 was decreased in both diseases. CSF τ _P−181 levels were significantly increased only in AD, but not in iNPH as compared with the controls. A cut-off level for τ _T at 300 pg/ml, successfully discriminated AD from normal aging with a 95.8% specificity and 91% sensitivity; whilst the τ _P-181/ τ _T ratio (cut-off value 0.169) was more specific (100%) but less sensitive (92.5%). For the discrimination of iNPH from AD τ _T achieved low specificity (77.8%) but high sensitivity (92.5%), whilst τ _P-181 (cut-off value 47.4) was both sensitive and specific (88.7% and 86.7% respectively) for the discrimination of these disorders. The present study, despite being clinical, supports the notion that CSF τ _P-181 alone or in combination with τ _T may be a useful marker in the discrimination of iNPH from AD.     

CSF biomarker profile and diagnostic value in vascular dementia

Background and purpose:  The differential diagnosis between vascular dementia (VD) and Alzheimer's disease (AD) or mixed dementia (MD) is not always easy in clinical practice. The purpose of the present study was to evaluate the cerebrospinal fluid (CSF) biomarkers tau protein in its total (τ_T) or hyperphosphorylated at threonin-181(τ_P-181) form and beta amyloid peptide 1–42 (Aβ42) alone and their combinations to investigate their diagnostic value in the discrimination between VD and AD or MD.
Methods:  The above CSF biomarkers were determined in duplicate and blind to the clinical diagnosis by double sandwich, enzyme-linked immunosorbent assay (ELISA) commercial kits (Innogenetics, Gent, Belgium) in 92 AD patients, 23 VD patients, 17 patients with MD and 68 controls.
Results:  Alzheimer's disease and MD showed increased levels of τ_T, τ_P and reduced levels of Aβ42 as compared with the controls. The best discrimination between VD and AD or MD was achieved by the combination of all three biomarkers, correctly classifying ≥85% of patients, either in the form of a discriminant function or in the form of the τ_T × τ_P-181/Aβ42 formula.
Conclusions:  Cerebrospinal fluid biomarkers may be a useful adjunct for the discrimination between AD/ MD and VD in every day clinical practice.     

Cerebrospinal fluid biochemical markers in early detection and in differential diagnosis of dementia disorders in routine clinical practice

Abstract. Measurement of total tau and amyloid _(1–42) (Ab42) in cerebrospinal fluid (CSF) improves diagnostic accuracy of Alzheimers disease (AD). We examined a consecutive patient sample referred to our center for diagnostic assessment of cognitive decline. CSF tau and A42 were assayed each week as routine neurochemical analyses. There were 119 patients investigated. These included 61 with probable AD (35 mild AD, 26 severe AD), 24 with mild cognitive impairment (MCI), 14 with vascular dementia, 11 with Lewy body dementia, and 9 with fronto-temporal dementia. Mild AD showed significantly lower CSF A42 levels and significantly higher CSF tau levels than the other diagnostic groups; 79% of MCI patients had pathological values for both biomarkers. We confirm that these biomarkers have a role in the clinical work-up of patients with cognitive deficits.     

Cerebrospinal fluid levels of total-tau, phospho-tau and Aβ42 predicts development of Alzheimer's disease in patients with mild cognitive impairment

Cerebrospinal fluid (CSF) biochemical diagnostic markers may be valuable to help in the diagnosis early in the course of Alzheimer's disease (AD), especially in the phase before clinically overt dementia, i.e. in patients with mild cognitive impairment (MCI). We studied 44 patients with MCI who, at 1-year follow-up investigation, had progressed to AD with dementia, and 32 controls. Three CSF biomarkers related to the central pathogenic processes in AD were analysed, including CSF total-tau (T-tau) (as a marker for neuronal degeneration), CSF phospho-tau (P-tau) (as a marker for hyperphosphorylation of tau and possibly for the formation of neurofibrillary tangles), and CSF Aβ42 (as a marker for Aβ metabolism, and possibly for the formation of senile plaques). At baseline, 35/44 (79.5%) of the MCI patients had high CSF T-tau, 31/44 (70.4%) high CSF P-tau, while 34/44 (77.3%) had low CSF-Aβ42 levels. The positive likelihood ratio was 8.45 for CSF T-tau, 7.49 for CSF P-tau and 8.20 for CSF Aβ42. These findings suggest that these CSF-markers are abnormal before the onset of clinical dementia, and that they may help to identify MCI patients that will progress to AD. CSF diagnostic markers will be especially important when drugs with potential effects on the progression of AD (e.g. γ-secretase inhibitors) will reach the clinical phase.     

The new Alzheimer’s criteria in a naturalistic series of patients with mild cognitive impairment

To test the validity of the new diagnostic criteria for Alzheimer’s disease (AD) in a naturalistic series of patients with mild cognitive impairment (MCI). Ninety consecutive MCI patients were enrolled in a longitudinal study on the natural history of cognitive impairment. Medial temporal (MT) atrophy on MRI was defined as hippocampal volume below the fifth percentile of the distribution in healthy elders, abnormal CSF was based on Sjogren’s cutoffs for Abeta42 and tau, and temporoparietal hypometabolism on 18F-FDG PET based on Herholz’s t sum score. Patients were followed clinically to detect conversion to AD (MCI-AD), non-AD dementia (MCI-nAD), or no conversion (MCI-NC). The 24 MCI-AD and 15 MCI-nAD patients had sociodemographic, clinical, and neuropsychological baseline features similar to the 51 MCI-NC patients. All MCI patients with MT atrophy converted to AD, as did all those with abnormal CSF, but only 48 and 35% of those without MT atrophy or abnormal CSF converted (p on logrank test = 0.0007 and 0.001). Prediction of AD conversion was enhanced when positivity to either MT atrophy or abnormal CSF was considered, with only 15% of those MCI patients negative on both converting to AD (p < 0.0005). Markers were not predictive of non-AD dementia conversion. The accuracy of either MT atrophy or abnormal CSF in discriminating MCI-AD from MCI-NC was good (AUC 0.82, 95% CI 0.70–0.95). MT atrophy and abnormal CSF are the single most robust predictors of conversion to AD in MCI patients, and their combination enhances prediction. AD markers are not predictive of conversion to non-AD dementia.     

Cerebrospinal fluid biomarkers in Progranulin mutations carriers

Cerebrospinal fluid (CSF) biomarkers (Aβ????, total tau, P-181 tau) are currently used to support a clinical diagnosis of Alzheimer's disease (AD). The CSF profile in frontotemporal lobar degeneration (FTLD) caused by Progranulin (GRN) mutation is unknown. We assessed CSF biomarkers in 145 AD, 140 FTLD (20 GRN positive, 120 GRN negative) patients, and 38 controls. Taking into account the reference values used in clinical practice, GRN mutation carriers and controls did not differ significantly for any biomarker, whereas GRN negative FTLD patients had higher tau levels than controls (p < 0.001) and patients carrying GRN Thr272fs mutation (p = 0.033, Chi-Square test). Comparing CSF biomarkers mean values among groups, total tau was significantly increased in GRN negative FTLD and in mutation carriers compared with controls (p < 0.001). P-181 tau CSF was increased in AD patients and in GRN negative FTLD compared with controls (p < 0.001), but not in 17 patients carrying the Thr272fs mutation. 88.2% of mutation carriers had normal CSF tau, despite the neurodegenerative nature of FTLD. Our results suggest that GRN mutation carriers have normal or borderline CSF biomarkers. In patients with an AD-like phenotype but normal or borderline CSF biomarkers, a diagnosis of FTLD-U caused by GRN mutations should be considered.     

Pittsburgh compound B-negative dementia: a possibility of misdiagnosis of patients with non-alzheimer disease-type dementia as having AD

Amyloid imaging has been used to detect amyloid deposition in the brain. We performed Pittsburgh compound B (PiB)-positron emission tomography on 63 patients with dementia having cognitive decline or memory disturbance. In addition, we measured the patients' apolipoprotein E4 (apo E4) status and cerebrospinal fluid (CSF) levels of amyloid-β (Aβ)1-42, tau, and P-tau. Finally, the patients were diagnosed as having probable Alzheimer disease (AD) on the basis of their neuropsychological findings and because they met the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria. Among the patients diagnosed with probable AD, 10 patients were PiB negative. The CSF levels of P-tau and tau in PiB-negative patients were significantly lower than those in the PiB-positive patients. In addition, the CSF levels of Aβ1-42 in the PiB-negative patients were significantly higher than those in the PiB-positive patients. None of the PiB-negative patients were apo E4 carriers. These results suggest that the PiB-negative patient group included not only AD patients but also non-AD-type dementia patients. However, our finding is based on a relatively small number of patients and therefore should be replicated in a larger cohort. In addition, it will be necessary to categorize these participants by longitudinal follow-up and postmortem pathological examinations.     

Relations between personality changes and cerebrospinal fluid biomarkers of Alzheimer's disease pathology

Specific changes in personality profiles may represent early non-cognitive symptoms of Alzheimer's disease (AD). Evaluating the subject's personality changes may add significant clinical information, as well as help to better understand the interaction between personality change, cognitive decline, and cerebral pathology. With this study we aimed to describe the relationship between personality changes and cerebrospinal fluid (CSF) markers of AD pathology at early clinical stages of the disease. One hundred and ten subjects, of whom 66 cognitively impaired patients (57 with mild cognitive impairment (MCI), and 9 with mild dementia) and 44 healthy controls, had neuropsychological examination as well as lumbar puncture to determine concentrations of CSF biomarkers of AD pathology (amyloid beta_1-42 (Aβ_1-42), phosphorylated tau (ptau-181), and total-tau (tau)). The Revised NEO Personality Inventory (NEO-PI-R) was administered twice, once to evaluate subjects' current personality and once to assess personality traits retrospectively 5 years before evaluation. Subjects with an AD CSF biomarker profile showed significant increase in neuroticism and decrease in conscientiousness over time as compared to non-AD CSF biomarker group. In regression analysis controlling for global cognition as measured by the MMSE score, increasing neuroticism and decreasing extraversion, openness to experience and conscientiousness were associated with lower Aβ_1-42 concentrations but not with tau and ptau-181 concentrations. Our findings suggest that early and specific changes in personality are associated with cerebral AD pathology. Concentrations of CSF biomarkers, additionally to severity of the cognitive impairment, significantly contribute in predicting specific personality changes.     

Maternal Family History is Associated with Alzheimer's Disease Biomarkers

A family history of Alzheimer's disease (AD) increases one's risk of developing late-onset AD (LOAD), and a maternal family history of LOAD influences risk more than a paternal family history. Accumulating evidence suggests that a family history of dementia associates with AD-typical biomarker changes. We analyzed cross-sectional data from non-demented, mild cognitive impairment (MCI), and LOAD participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) with PET imaging using Pittsburgh Compound B (PiB, n = 99) and cerebrospinal fluid (CSF) analysis (n = 403) for amyloid-β peptide (Aβ) and total tau. We assessed the relationship of CSF and PiB biomarkers and family history of dementia, as well as parent gender effects. In the larger analysis of CSF biomarkers, we assessed diagnosis groups individually. In the overall sample, CSF Aβ, tau/Aβ ratio, and global PiB uptake were significantly different between family history positive and negative groups, with markers of increased AD burden associated with a positive maternal family history of dementia. Moreover, a maternal family history of dementia was associated with significantly greater PiB Aβ load in the brain in the parietal cortex, precuneus, and sensorimotor cortex. Individuals with MCI positive for a maternal family history of dementia had significantly more markers of AD pathophysiology than individuals with no family history of dementia. A family history of dementia is associated with AD-typical biomarker changes. These biomarker associations are most robust in individuals with a maternal family history, suggesting that a maternally inherited factor influences AD risk.     

Grey matter volume correlates of cerebrospinal markers of Alzheimer-pathology in Parkinson's disease and related dementia

Regional brain grey matter volume (GMV) reductions and abnormal cerebrospinal fluid (CSF) levels of τ and Aβ, extensively studied as biomarkers of Alzheimer's disease (AD), have also been reported in Parkinson's disease (PD) and related dementia (PDD). However, the relationship between these CSF and MRI biomarkers in PD and PDD remains unexplored. We studied these associations in 33 PD patients (18 with no dementia [PDND]; 15 fulfilling PDD criteria) and 12 neurologically unimpaired controls, with neuropsychological assessment, CSF ELISA studies, and voxel-based morphometry (VBM) analysis of high-field brain MRI. Neuropsychological assessment showed a gradation in cognitive performance from controls to PDND (significantly worse on visuospatial performance) and then to PDD (more impaired on memory, naming, fluency and visuospatial functions). No CSF-VBM correlations were found in controls or PDND patients. In contrast, in the analysis of both the PDD subgroup and the entire PD (PDND + PDD) sample, we found significant negative CSF-GMV correlations for τ and phospho-τ and significant positive CSF-GMV correlations for Aβ in mostly frontal and temporal structures. The correlations in the entire PD sample fitted with a linear model and were thus unlikely to have been driven solely by the PDD subgroup. Additionally, an association between both the CSF markers and the CSF-associated GMV reductions with several neuropsychological functions was found. We interpret that CSF markers of AD pathology are associated with VBM-measures of brain atrophy in PD-related dementia and within the PD cognitive continuum, and deserve further attention as putative biomarkers of cognitive impairment and dementia in PD.     

The Alzheimer's Disease Neuroimaging Initiative: Progress report and future plans

The Alzheimer's Disease Neuroimaging Initiative (ADNI) beginning in October 2004, is a 6-year research project that studies changes of cognition, function, brain structure and function, and biomarkers in elderly controls, subjects with mild cognitive impairment, and subjects with Alzheimer's disease (AD). A major goal is to determine and validate MRI, PET images, and cerebrospinal fluid (CSF)/blood biomarkers as predictors and outcomes for use in clinical trials of AD treatments. Structural MRI, FDG PET, C-11 Pittsburgh compound B (PIB) PET, CSF measurements of amyloid β (Aβ) and species of tau, with clinical/cognitive measurements were performed on elderly controls, subjects with mild cognitive impairment, and subjects with AD. Structural MRI shows high rates of brain atrophy, and has high statistical power for determining treatment effects. FDG PET, C-11 Pittsburgh compound B PET, and CSF measurements of Aβ and tau were significant predictors of cognitive decline and brain atrophy. All data are available at UCLA/LONI/ADNI, without embargo. ADNI-like projects started in Australia, Europe, Japan, and Korea. ADNI provides significant new information concerning the progression of AD.     

Cerebrospinal tau,phospho‐tau,and beta‐amyloid and neuropsychological functions in Parkinson's disease

Alzheimer's disease (AD)‐pathology may play a role in Parkinson's disease (PD)‐related dementia (PDD). The aim of this study was to assess cerebrospinal fluid (CSF) levels of tau, phospho‐tau, and beta‐amyloid, proposed AD biomarkers, and their relationship with cognitive function in PD. Forty PD patients [20 nondemented (PDND); 20 PDD] and 30 controls underwent CSF tau, phospho‐tau, and beta‐amyloid analysis using specific ELISA techniques. All PD patients and 15 controls underwent neuropsychological testing of fronto‐subcortical (attention, fluency) and neocortical (memory, naming, visuoperceptive) functions. CSF markers levels were compared between groups, and compared and correlated with neuropsychological measures in PDND and PDD separately and as a continuum (PD). CSF tau and phospho‐tau were higher in PDD than in PDND and controls (P < 0.05). CSF beta‐amyloid ranged from high (controls) to intermediate (PDND) and low (PDD) levels (P < 0.001). In all PD and PDD patients, high CSF tau and phospho‐tau were associated with impaired memory and naming. In PDND, CSF beta‐amyloid was related with phonetic fluency. These findings suggest underlying AD‐pathology in PDD in association with cortical cognitive dysfunction, and that low CSF beta‐amyloid in PDND patients with impaired phonetic fluency can constitute an early marker of cognitive dysfunction. © 2009 Movement Disorder Society     

CSF phosphorylated tau—does it constitute an accurate biological test for Alzheimer's disease?

INTRODUCTION: There is considerable interest in developing a diagnostic test which could differentiate between early Alzheimer's disease (AD) and other causes of memory impairment with more than 80% sensitivity and 80% specificity. OBJECTIVE: To review the studies that have examined CSF phosphorylated tau as diagnostic test of AD vs clinically representative comparison groups. METHOD: A critical review of the literature using Embase, Web of Science, Medline and Psychinfo databases supplemented by handsearching and contact with experts in the field. RESULTS: CSF phosphorylated tau is a marker of AD that improves upon the utility of CSF total tau and clinical examination alone. Studies have found high levels of tau phosphorylated at Threonine 231 and/or Serine 199 in AD but not in other causes of dementia, in depression or in healthy elderly controls. Of particular interest, the test appears equally valid in cases of early AD as in moderate or late stages and may also be of use in predicting future decline in subjects with mild cognitive impairment. CONCLUSION: CSF phosphorylated tau is a promising diagnostic test for AD but this requires replication using pathologically confirmed cases.     

Diagnosing the mild cognitive impairment stage of Alzheimer's disease]

Recently, it has become important to diagnose Alzheimer's Disease (AD) at an early stage due to the development of AD therapy. Also, there is increasing recognition of a class of elderly people with complaints of memory loss but who nevertheless do not meet the criteria for dementia. "Mild cognitive impairment" (MCI) is the term used for this disorder, and amnestic MCI is highly converted to AD. In this study we evaluated the accuracy of diagnosis of amnestic MCI by cerebrospinal fluid total-tau protein (CSF/total-tau), cerebrospinal fluid amyloid beta 1-42 protein (CSF/A beta 1-42), and cerebral blood flow in the posterior cingulate cortex using SPECT. CSF/total-tau was the most appropriate to discriminate between normal cognitive individuals and those with amnestic MCI. We also evaluated the CSF/total-tau and MRI images between patients with stable MCI and those with progressive MCI, including those who converted to AD in the following two years. The stable type was characterized by normal CSF/total-tau levels and relatively high grade periventricular white matter lesions (PWML). Conversely, the progressive type was characterized by high CSF-tau levels and relatively low grade PWML. We speculate that stable MCI is due to ischemic change with in the white matter lesion, while progressive MCI may represent a previous stage of AD.     

Cerebrospinal fluid tau and amyloid β42 protein in patients with myotonic dystrophy type 1

Background:  Myotonic dystrophy type 1 (DM1) is associated with brain morphology changes including neurofibrillary degeneration.
Methods:  We have examined cerebrospinal fluid (CSF) markers indicative of neuronal degeneration and amyloidogenesis; total tau (T-tau), phosphorylated tau (P-tau) and β amyloid_1–42 (Aβ42), in 32 patients with DM1.
Results and conclusions:  Associations between CSF markers and CTG repeat expansion size, brain MRI findings, and neuropsychological test results were analysed. As compared with matched controls Aβ42 was significantly decreased ( P  = 0.001), whilst levels of T-tau were increased ( P  < 0.001). No difference was found between measures considering P-tau levels. At present the clinical implications of these findings is unclear, because of an overlap between CSF values of DM1 patients and healthy controls, but also regarding modest associations between CSF markers and other measures. However notably, the Tau pathology, as seen in DM1, differs from Alzheimers disease, considering the lack of increased levels of P-tau.     

CSF phosphorylated tau protein and mild cognitive impairment: a prospective study

Cerebrospinal fluid (CSF) tau protein phosphorylated at both Thr231 and Ser235 sites (CSF/phospho-tau(231-235)) and total tau (CSF/total-tau) were quantified by sandwich ELISA in 20 patients with mild cognitive impairment (MCI) who eventually developed AD on follow-up as well as seven memory complainers with no objective memory loss. 13/20 (65%) of the MCI patients had high CSF/total-tau and detectable levels of CSF/phospho-tau(231-235), whereas these markers were low and under a detectable level in all of the memory complainers. Although either a total-tau, phospho-tau measurement or a combination of these can help in predicting if MCI will develop AD, our results suggest that the pathogenic steps of AD may be at the stage that finally leads to an accumulation of abnormally phosphorylated tau and neuron death, at least in some brain areas, when MCI patients present with the earliest detectable clinical symptoms of dementia.     

CSF and clinical hallmarks of subcortical dementias: focus on DLB and PDD

Dementia has become a relevant problem associated with the elderly in our countries. Increased interest in the field has yielded a copious literature, so far mostly centered on Alzheimer's dementia. Cerebrospinal fluid (CSF) analysis combined with neuropsychology, even in absence of neuroimaging, represents the gold standard to reach a diagnosis when cortical cognitive impairment prevails. In view of this, low levels of CSF amyloid peptides β (Aβ) and high tau/Aβ protein ratio, despite prominent impairment of executive functions or concomitant vascular burden, facilitate the diagnosis of Alzheimer's disease. Conversely, an early cognitive impairment occurring in patients suffering from Parkinson's disease (PD) or Lewy body disorders (LBDs), both diagnoses posed on pure clinical grounds, remains quite elusive in term of biomarkers or neuropsychological assessment. Whether PD with dementia (PDD) and dementia with Lewy bodies (DLB) represent further steps along with a continuum of the same progressive degeneration due to Lewy bodies deposition, rather then the association of Lewy bodies and Aβ pathology, remains a challenging issue. Aim of this work is to set a state-of-the-art on the neuropsychological profiles of both or DLB. Then, we will focus on the ongoing controversies about the specificity of the standard CSF biomarkers if applied to extrapyramidal disorders. Our conclusions are that the CSF pattern, in PDD and DLB, can certainly be distinct from that in AD, though mechanisms leading to dementia could be shared among them. It is possible that, by combining imaging tracers, neuropsychologically careful assessment and renewed CSF biomarkers, DLB can be better distinguished in subgroups, depending on the presence or absence of a relevant amyloid burden. However, more complete data, possibly collected in fieri during the progressive derangement of cognitive abilities, are needed to improve our ability to decipher and treat these entities.     

Elevation of 12/15 lipoxygenase products in AD and mild cognitive impairment

The 12/15 lipoxygenase (12/15LOX) enzyme is increased in pathologically affected frontal and temporal regions of Alzheimer's disease (AD) brains compared with controls. Herein, we measured 12(S)-HETE and 15(S)-HETE levels, products of 12/15LOX, in cerebrospinal fluid (CSF) of normal individuals, subjects with mild cognitive impairment (MCI) and AD. Compared with controls, there was a significant increase of both metabolites in CSF from AD and MCI, which correlated with lipid peroxidation and tau protein levels. These results suggest that the activation of this enzyme occurs early in the course of AD, before the onset of overt dementia, thereby implicating 12/15LOX-mediated lipid peroxidation in the pathogenesis of AD.     

The neurofilament heavy chain (NfH) in the cerebrospinal fluid diagnosis of Alzheimer's disease

BACKGROUND/AIMS: Attempting to improve the cerebrospinal fluid (CSF) diagnosis of Alzheimer's disease (AD), the neurofilament heavy chain isoform, NfH(SMI35) was compared to other CSF markers [total tau, phospho-tau, amyloid beta 1-42 (Abeta42), the ratio of amyloid beta fragments Abeta42/Abeta40 (Abeta ratio)]. METHODS: CSF levels were determined in patients with AD (n = 109), mild cognitive impairment (MCI, n = 25), frontotemporal dementia (n = 15), vascular dementia (VD, n = 41), and controls (n = 58). RESULTS: CSF NfH(SMI35) was elevated in AD and VD as compared to controls (p < 0.05). Total tau was higher in AD as compared to controls (p < 0.05). CSF phospho-tau was elevated in AD as compared to controls and VD (p < 0.05 each). CSF Abeta42 and Abeta ratios in AD were lower than in MCI and controls (p < 0.05 each). CONCLUSION: The diagnostic potential of NfH(SMI35) is not superior to that of other CSF markers.