Skip to main content

Longitudinal Cognitive and Biomarker Measurements Support a Unidirectional Pathway in Alzheimer's Disease Pathophysiology

Go to Publication »

Biol Psychiatry. 2020 Jul 12:S0006-3223(20)31739-X. doi: 10.1016/j.biopsych.2020.06.029. Online ahead of print.


BACKGROUND: Amyloid-β (Aβ) likely plays a primary role in Alzheimer’s disease pathogenesis, but longitudinal Aβ, tau, and neurodegeneration (A/T/N) measurements in the same individuals have rarely been examined to verify the temporal dynamics of these biomarkers.

METHODS: In this study, we investigated the temporal ordering of Aβ, tau, and neurodegeneration using longitudinal biomarkers in nondemented elderly individuals. A total of 395 cognitively unimpaired individuals and 204 individuals with mild cognitive impairment (320 [53%] were female) were classified into 8 A±/T±/N± categories according to the abnormal (+)/normal (-) status of Aβ (18F-florbetapir or 18F-florbetaben) positron emission tomography (PET), 18F-flortaucipir PET, and adjusted hippocampal volume (aHCV). Follow-up Aβ PET, tau PET, and aHCV measurements at 0.6 to 4.1 years were available for 35% to 63% of the sample. Baseline Aβ, tau, and aHCV were compared between different A/T/N profiles. We investigated the associations of baseline and longitudinal Aβ, tau, and neurodegeneration in relation to one another continuously.

RESULTS: Among T- participants, tau was higher for A+/T-/N- individuals compared with the A-/T-/N- group (p = .02). Among N- participants, neurodegeneration was worse among A+/T+/N- individuals compared with the A-/T-/N- group (p = .001). High baseline Aβ was associated (p < .001) with subsequent tau increase and high baseline tau was associated (p = .002) with subsequent aHCV decrease, whereas high tau and low aHCV at baseline were not associated with subsequent Aβ increase.

CONCLUSIONS: These findings define a sequence of pathological events in Alzheimer’s disease that support a current model of Alzheimer’s disease pathogenesis in which Aβ appears early, followed by deposition of abnormal tau aggregates and subsequent neurodegeneration.

PMID:32919611 | DOI:10.1016/j.biopsych.2020.06.029

Read More »