Cerebrospinal Fluid Beta-Amyloid 42 Is Reduced before the Onset of Sporadic Dementia: A Population-Based Study in 85-Year-OldsSkoog I. · Davidsson P. · Aevarsson Ó. · Vanderstichele H. · Vanmechelen E. · Blennow K.
aInstitute of Clinical Neuroscience, Unit of Neuropsychiatric Epidemiology, University of Göteborg, Sahlgrenska University Hospital, Göteborg, bInstitute of Clinical Neuroscience, Department of Experimental Neuroscience, Unit of Neurochemistry, University of Göteborg, Sahlgrenska University Hospital, Mölndal, and cThe Medical Research Council, Sweden; dInnogenetics, Ghent, Belgium
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.