Evaluation of Plasma Aβ as Predictor of Alzheimer's Disease in Older Individuals Without Dementia: A Population-Based Study

Article type: Research Article

Authors: Hansson, Oskar^{a; b; *} | Stomrud, Erik^{a; b; *} | Vanmechelen, Eugeen^c | Östling, Svante^d | Gustafson, Deborah R^d | Zetterberg, Henrik^d | Blennow, Kaj^d | Skoog, Ingmar^d

Affiliations: [a] Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Sweden | [b] Neuropsychiatric Clinic, Skåne University Hospital, Malmö, Sweden | [c] Innogenetics NV, Ghent, Belgium | [d] Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska University Hospital, University of Gothenburg, Sweden

Correspondence: [*] Correspondence to: Oskar Hansson, MD, Ph.D. or Erik Stomrud, MD, PhD, Neuropsychiatric Clinic, Skåne University Hospital, S-20502 Malmö, Sweden. Tel.: +46 40 335036; Fax: +46 40 334604; E-mail: [email protected] or [email protected].

Abstract: Amyloid-β (Aβ) pathology is a major component in the mechanisms behind Alzheimer's disease (AD). Measurement of Aβ42 in cerebrospinal fluid predicts cognitive decline in patients with mild cognitive impairment and identifies AD in patients with dementia. However, studies on Aβ in plasma are contradictory. In this prospective population-based study, plasma Aβ42 and Aβ40 were measured at baseline in 730 adults aged 70 years or older and without dementia. After five years, plasma levels were analyzed again and participants were assessed for development of dementia. During follow-up, 53 individuals (7%) developed dementia of which 37 (5%) were classified as AD. No difference in baseline plasma Aβ42, Aβ40, or Aβ42/Aβ40 ratio levels were observed between converters to dementia or AD compared to the cognitively stable individuals. However, individuals with plasma Aβ40 levels above the median level for the group at baseline had an increased risk of developing dementia and AD during the follow-up, even after adjustment for age, gender, APOE genotype, and educational level (odds ratio = 2.2, 95% confidence interval = 1.0–4.7, p < 0.05). Neither plasma Aβ42 nor the Aβ42/Aβ40 ratio influenced the risk of developing dementia or AD. Moreover, Aβ42 and Aβ40 levels increased over the 5 years, whereas the Aβ42/Aβ40 ratio decreased (p < 0.001). In conclusion, this study suggests that measurement of plasma Aβ should not be used clinically to predict dementia or AD. However, plasma Aβ40 may possibly be regarded as a moderate risk marker comparable to other risk markers for AD such as first-degree family history of dementia.

Keywords: Alzheimer's disease, amyloid-β 40, amyloid-β 42, biological markers, cohort studies, dementia, plasma

DOI: 10.3233/JAD-2011-111418

Journal: Journal of Alzheimer's Disease, vol. 28, no. 1, pp. 231-238, 2012