Cerebral Amyloidosis in Individuals with Subjective Cognitive Decline: From Genetic Predisposition to Actual Cerebrospinal Fluid Measurements

TL;DR

This study finds that cerebral amyloidosis, either genetically predicted or measured in cerebrospinal fluid, is linked to subjective cognitive decline, but tau levels are not.

Contribution

The study identifies a specific link between cerebral amyloidosis and subjective cognitive decline using both genetic and fluid biomarkers.

Findings

Abnormal CSF Aβ42 levels are associated with 2.5-fold higher odds of SCD.

Higher polygenic loading for Aβ42 is linked to 1.6-fold higher odds of SCD.

CSF Tau and polygenic Tau loading show no association with SCD.

Abstract

The possible relationship between Subjective Cognitive Decline (SCD) and dementia needs further investigation. In the present study, we explored the association between specific biomarkers of Alzheimer’s Disease (AD), amyloid-beta 42 (Aβ42) and Tau with the odds of SCD using data from two ongoing studies. In total, 849 cognitively normal (CN) individuals were included in our analyses. Among the participants, 107 had available results regarding cerebrospinal fluid (CSF) Aβ42 and Tau, while 742 had available genetic data to construct polygenic risk scores (PRSs) reflecting their genetic predisposition for CSF Aβ42 and plasma total Tau levels. The associations between AD biomarkers and SCD were tested using logistic regression models adjusted for possible confounders such as age, sex, education, depression, and baseline cognitive test scores. Abnormal values of CSF Aβ42 were related to 2.5-fold higher odds of SCD, while higher polygenic loading for Aβ42 was associated with 1.6-fold higher odds of SCD. CSF Tau, as well as polygenic loading for total Tau, were not associated with SCD. Thus, only cerebral amyloidosis appears to be related to SCD status, either in the form of polygenic risk or actual CSF measurements. The temporal sequence of amyloidosis being followed by tauopathy may partially explain our findings.

Figures