Institute for Clinical and Translational Science

Objective

To elucidate the relationship between the two hallmark proteins of Alzheimer's disease (AD), amyloid-β (Aβ) and tau, and clinical decline over time among cognitively normal older individuals.

A longitudinal cohort of clinically and cognitively normal older individuals assessed with baseline lumbar puncture and longitudinal clinical assessments.

Research centers across the United States and Canada.

We examined one hundred seven participants with a Clinical Dementia Rating (CDR) of 0 at baseline examination.

Using linear mixed effects models, we investigated the relationship between CSF p-tau_181p, CSF Aβ_1-42 and clinical decline as assessed using longitudinal change in global CDR, CDR-Sum of Boxes (CDR-SB), and the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog).

We found a significant relationship between decreased CSF Aβ_1-42 and longitudinal change in global CDR, CDR-SB, and ADAS-cog in individuals with elevated CSF p-tau_181p. In the absence of CSF p-tau_181p, the effect of CSF Aβ_1-42 on longitudinal clinical decline was not significantly different from zero.

In cognitively normal older individuals, Aβ-associated clinical decline over a mean of three years may occur only in the presence of ongoing, “downstream” neurodegeneration.