CSF Aβ 42 levels correlate with amyloid-neuropathology in a population-based autopsy study

Abstract

Objective: To investigate the relationship of amyloid neuropathology to postmortem CSF Aβ 42 levels in an autopsy sample of Japanese American men from the population-based Honolulu–Asia Aging Study.

Methods: In 1991, participants were assessed and diagnosed with dementia (including subtype) based on published criteria. At death CSF was obtained from the ventricles. Neuritic plaques (NP) and diffuse plaques in areas of the neocortex and hippocampus were examined using Bielschowsky silver stains. Cerebral amyloid angiopathy (CAA) was measured by immunostaining for β4 amyloid in cerebral vessels in the neocortex. Neuropathologically confirmed AD was diagnosed using Consortium to Establish a Registry for Alzheimer’s Disease criteria. In 155 autopsy samples, log transformed linear regression models were used to examine the association of NP and CAA to Aβ 42 levels, controlling for clinical dementia severity, time between diagnosis and death, age at death, brain weight, hours between death and collection of CSF, education, and APOE genotype.

Results: Higher numbers of NP in the neocortex (p trend = 0.001) and in the hippocampus (p trend = 0.03) were strongly associated with lower levels of Aβ 42. Individuals with CAA had lower Aβ 42 levels (β coefficient = −0.48; 95% CI −0.9, −0.1). Compared to participants with a diagnosis of clinical dementia, those with pathologically confirmed AD had lower Aβ 42 levels (β coefficient = −0.74; 95% CI −1.4, −0.1).

Conclusion: The current study suggests that lower Aβ 42 levels reflect neuropathologic processes implicated in amyloid-related pathologies, such as NP and CAA.