CSF Aβ42, Tau and phosphorylated Tau, APOE ɛ4 allele and MCI type in progressive MCI

Abstract Background The patients with mild cognitive impairment (MCI) have an elevated risk for Alzheimer's disease (AD). Especially the amnestic MCI is seen as prodrome of AD. Apolipoprotein E (APOE) ɛ4 allele, abnormal CSF Aβ42, Tau and phosphorylated Tau (phospho-Tau) levels are associated with elevated risk for AD. Methods APOE genotyping was done by PCR based method and baseline CSF Aβ42, Tau and phospho-Tau were measured by ELISA from 60 controls and 79 MCI patients. Results Thirty-three MCI patients developed dementia during an average of 3.5 years follow-up. CSF Aβ42 was decreased and Tau and phospho-Tau were increased in the progressive MCI patients. The APOE ɛ4 allele was more frequent in the progressive MCI patients. The APOE ɛ4 allele showed a dose dependent association to the Aβ42 levels in the progressive MCI patients and to all of the markers in controls. Conclusions Decreased CSF Aβ42 and elevated Tau or phospho-Tau together with APOE ɛ4 allele are highly predictive for the dementia in MCI patients with amnestic or executive symptoms.

[1]  R Brookmeyer,et al.  Visual memory predicts Alzheimer’s disease more than a decade before diagnosis , 2003, Neurology.

[2]  J. Morris,et al.  Pathologic correlates of nondemented aging, mild cognitive impairment, and early-stage alzheimer’s disease , 2001, Journal of Molecular Neuroscience.

[3]  H. Amièva,et al.  Annual Rate and Predictors of Conversion to Dementia in Subjects Presenting Mild Cognitive Impairment Criteria Defined according to a Population-Based Study , 2004, Dementia and Geriatric Cognitive Disorders.

[4]  D. Bennett,et al.  Vitamin E and donepezil for the treatment of mild cognitive impairment. , 2005, The New England journal of medicine.

[5]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[6]  H. Feldman,et al.  Apolipoprotein E ε4 genotype as a risk factor for cognitive decline and dementia: data from the Canadian Study of Health and Aging , 2004, Canadian Medical Association Journal.

[7]  T. Teramoto,et al.  Determination by PCR-RFLP of apo E genotype in a Japanese population. , 1993, The Journal of laboratory and clinical medicine.

[8]  S. DeKosky,et al.  Mild cognitive impairment, amnestic type , 2004, Neurology.

[9]  Kaj Blennow,et al.  Cerebrospinal fluid levels of total‐tau, phospho‐tau and Aβ42 predicts development of Alzheimer's disease in patients with mild cognitive impairment , 2003 .

[10]  H. Arai,et al.  Cerebrospinal fluid tau protein and periventricular white matter lesions in patients with mild cognitive impairment: implications for 2 major pathways. , 2004, Archives of neurology.

[11]  E. Kaplan,et al.  The Boston naming test , 2001 .

[12]  N. Foster,et al.  Mild cognitive impairments predict dementia in nondemented elderly patients with memory loss. , 2001, Archives of neurology.

[13]  J. Haines,et al.  Effects of Age, Sex, and Ethnicity on the Association Between Apolipoprotein E Genotype and Alzheimer Disease: A Meta-analysis , 1997 .

[14]  M. Pericak-Vance,et al.  Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[15]  R. Mohs,et al.  Consortium to establish a registry for Alzheimer's disease (CERAD) clinical and neuropsychological assessment of Alzheimer's disease. , 2002, Psychopharmacology bulletin.

[16]  J. Haines,et al.  Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. , 1997, JAMA.

[17]  C. Jack,et al.  Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment , 1999, Neurology.

[18]  D. Selkoe Alzheimer's disease: genes, proteins, and therapy. , 2001, Physiological reviews.

[19]  D. Schaid,et al.  Apolipoprotein E status as a predictor of the development of Alzheimer's disease in memory-impaired individuals. , 1995, JAMA.

[20]  C. Jack,et al.  Mild cognitive impairment can be distinguished from Alzheimer disease and normal aging for clinical trials. , 2004, Archives of neurology.

[21]  D. Royall,et al.  Misclassification Is Likely in the Assessment of Mild Cognitive Impairment , 2004, Neuroepidemiology.

[22]  Charles DeCarli,et al.  Cerebrospinal fluid tau and beta-amyloid: how well do these biomarkers reflect autopsy-confirmed dementia diagnoses? , 2003, Archives of neurology.

[23]  N Butters,et al.  Episodic and semantic memory: a comparison of amnesic and demented patients. , 1987, Journal of clinical and experimental neuropsychology.

[24]  K. Blennow,et al.  CSF Aβ 42 levels correlate with amyloid-neuropathology in a population-based autopsy study , 2003, Neurology.

[25]  J. Morris,et al.  The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assesment of Alzheimer's disease , 1989, Neurology.

[26]  A Drzezga,et al.  Cerebrospinal fluid tau and beta-amyloid 42 proteins identify Alzheimer disease in subjects with mild cognitive impairment. , 2002, Archives of neurology.

[27]  F. Schmitt,et al.  Alzheimer neuropathologic alterations in aged cognitively normal subjects. , 1999, Journal of neuropathology and experimental neurology.

[28]  J. Price,et al.  Mild cognitive impairment represents early-stage Alzheimer disease. , 2001, Archives of neurology.

[29]  Roberta F. White,et al.  The preclinical phase of alzheimer disease: A 22-year prospective study of the Framingham Cohort. , 2000, Archives of neurology.

[30]  H. Möller,et al.  Value of CSF β-amyloid1–42 and tau as predictors of Alzheimer's disease in patients with mild cognitive impairment , 2004, Molecular Psychiatry.

[31]  K. Blennow,et al.  Cerebrospinal Fluid Beta-Amyloid 42 Is Reduced before the Onset of Sporadic Dementia: A Population-Based Study in 85-Year-Olds , 2003, Dementia and Geriatric Cognitive Disorders.

[32]  P. Deyn,et al.  Improved discrimination of AD patients using β-amyloid(1-42) and tau levels in CSF , 1999, Neurology.

[33]  J. Morris,et al.  Current concepts in mild cognitive impairment. , 2001, Archives of neurology.

[34]  G. Ratcliff,et al.  Preclinical Alzheimer disease , 2004, Neurology.

[35]  T. Lehtimäki,et al.  Apolipoprotein E phenotypes in Finnish youths: a cross-sectional and 6-year follow-up study. , 1990, Journal of lipid research.

[36]  R. Reitan Validity of the Trail Making Test as an Indicator of Organic Brain Damage , 1958 .

[37]  J. Morris The Clinical Dementia Rating (CDR) , 1993, Neurology.

[38]  J. Schneider,et al.  Mild cognitive impairment is related to Alzheimer disease pathology and cerebral infarctions , 2005, Neurology.

[39]  B. Reisberg,et al.  Mild cognitive impairment in the elderly , 1991, Neurology.

[40]  Elbert W. Russell,et al.  A multiple scoring method for the assessment of complex memory functions. , 1975 .

[41]  Ranjan Duara,et al.  Conversion to Dementia among Two Groups with Cognitive Impairment , 2004, Dementia and Geriatric Cognitive Disorders.

[42]  M. Albert,et al.  MRI measures of entorhinal cortex vs hippocampus in preclinical AD , 2002, Neurology.

[43]  J. Haines,et al.  Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. , 1993, Science.

[44]  H. Soininen,et al.  Hippocampus and entorhinal cortex in mild cognitive impairment and early AD , 2004, Neurobiology of Aging.

[45]  E. Reiman,et al.  Vascular risk factors, incidence of MCI, and rates of progression to dementia , 2004, Neurology.

[46]  Arthur L. Benton,et al.  Word fluency and brain damage , 1967 .

[47]  C. Broeckhoven,et al.  Evaluation of breast cancer risk assessment packages in the family history evaluation and screening programme , 2003, Journal of medical genetics.

[48]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[49]  Holly Soares,et al.  Cerebrospinal fluid β-amyloid1–42 and tau in control subjects at risk for Alzheimer’s disease: The effect of APOE ε4 allele , 2004, Biological Psychiatry.

[50]  Ian G. McKeith,et al.  Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales , 2001, The Lancet.

[51]  Dc Washington Diagnostic and Statistical Manual of Mental Disorders, 4th Ed. , 1994 .

[52]  D. Harvey,et al.  Memory impairment, but not cerebrovascular disease, predicts progression of MCI to dementia , 2004, Neurology.

[53]  P. Visser,et al.  Predictive Accuracy of MCI Subtypes for Alzheimer’s Disease and Vascular Dementia in Subjects with Mild Cognitive Impairment: A 2-Year Follow-Up Study , 2005, Dementia and Geriatric Cognitive Disorders.

[54]  J. Thornby,et al.  Longitudinal analysis of abnormal domains comprising mild cognitive impairment (MCI) during aging , 2002, Journal of the Neurological Sciences.

[55]  R. Palmer,et al.  Executive Control Mediates Memory's Association with Change in Instrumental Activities of Daily Living: The Freedom House Study , 2005, Journal of the American Geriatrics Society.

[56]  J. Kaye,et al.  High cerebrospinal fluid tau and low amyloid beta42 levels in the clinical diagnosis of Alzheimer disease and relation to apolipoprotein E genotype. , 1998, Archives of neurology.

[57]  Hilkka Soininen,et al.  CSF Aβ42 and tau or phosphorylated tau and prediction of progressive mild cognitive impairment , 2005, Neurology.

[58]  Henrik Zetterberg,et al.  APOE ε4 allele is associated with reduced cerebrospinal fluid levels of Aβ42 , 2004, Neurology.

[59]  Margaret A. Pericak-Vance,et al.  Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease , 1997 .