Cerebrospinal fluid beta-amyloid 42 is reduced before the onset of sporadic dementia: a population-based study in 85-year-olds |
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Authors: | Skoog I Davidsson P Aevarsson O Vanderstichele H Vanmechelen E Blennow K |
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Institution: | Institute of Clinical Neuroscience, Unit of Neuropsychiatric Epidemiology, University of G?teborg, Sahlgrenska University Hospital, G?teborg, Sweden. |
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Abstract: | Deposition of beta-amyloid (Abeta) is an early pathogenic event in Alzheimer's disease (AD). We measured Abeta42 and Abeta40 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 Abeta42 (p = 0.001) and Abeta40 (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- Abeta42 (p = 0.003), but not CSF-Abeta40 (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-Abeta42, while none of those in the highest 33rd percentile of CSF-Abeta42 developed dementia during follow-up. There were no significant differences between carriers and non-carriers of the apolipoprotein E epsilon4 allele regarding CSF-Abeta42 or CSF-Abeta40. Our study suggests that low CSF-Abeta42 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 Abeta, specifically involving Abeta42, before the onset of clinical symptoms in AD. |
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