Cerebrospinal Fluid Beta-Amyloid 42 Is Reduced before the Onset of Sporadic Dementia: A Population-Based Study in 85-Year-Olds

• Published in: Dementia and geriatric cognitive disorders 2003-01, Vol.15 (3), p.169-176
• Main Authors: Skoog, I., Davidsson, P., Aevarsson, Ó., Vanderstichele, H., Vanmechelen, E., Blennow, K.
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - cerebrospinal fluid; Amyloid beta-Peptides - cerebrospinal fluid; Apolipoproteins E - genetics; Biological and medical sciences; Brain - pathology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dementia; Dementia - cerebrospinal fluid; Female; Follow-Up Studies; Humans; Male; Medical sciences; Neurology; Original Research Article; Peptide Fragments - cerebrospinal fluid; Population Surveillance; Protein Isoforms - genetics; Risk Factors; Sampling Studies
• ISSN: 1420-8008; 1421-9824
• DOI: 10.1159/000068478

Deposition of β-amyloid (Aβ) is an early pathogenic event in Alzheimer’s disease (AD). We measured Aβ42 and Aβ40 in cerebrospinal fluid (CSF) in a population-based sample of 85-year-olds, 27 demented and 35 non-demented. During the following 3 years, 7 of the 35 non-demented individuals had developed dementia, while 28 remained non-demented. Reduced CSF levels of both Aβ42 (p = 0.001) and Aβ40 (p = 0.0001) were found in patients with manifest AD and vascular dementia at the age of 85. Non-demented individuals who developed dementia during follow-up had lower levels of CSF- Aβ42 (p = 0.003), but not CSF-Aβ40 (p = 0.96), than those who remained non-demented. The odds ratio for development of dementia was 8.2 (p = 0.027) for individuals in the lower 50th percentile of CSF-Aβ42, while none of those in the highest 33rd percentile of CSF-Aβ42 developed dementia during follow-up. There were no significant differences between carriers and non-carriers of the apolipoprotein E Ε4 allele regarding CSF-Aβ42or CSF-Aβ40.Our study suggests that low CSF-Aβ42 is found also in an unselected population-based sample of old demented patients and provides the first evidence of a disturbance in the metabolism of Aβ, specifically involving Aβ42, before the onset of clinical symptoms in AD.