Microglial activation and tau burden predict cognitive decline in Alzheimer’s disease

Publication: Brain A Journal of Neurology

Maura Malpetti, Rogier A Kievit, Luca Passamonti, P Simon Jones, Kamen A Tsvetanov, Timothy Rittman, Elijah Mak, Nicolas Nicastro, W Richard Bevan-Jones, Li Su, Young T Hong, Tim D Fryer, Franklin I Aigbirhio, John T O’Brien, James B Rowe

7 May 2020


Tau pathology, neuroinflammation, and neurodegeneration are key aspects of Alzheimer’s disease. Understanding whether these features predict cognitive decline, alone or in combination, is crucial to develop new prognostic measures and enhanced stratification for clinical trials. Here, the researchers studied how baseline assessments of in vivo tau pathology (measured by 18F-AV-1451 PET), neuroinflammation (measured by 11C-PK11195 PET) and brain atrophy (derived from structural MRI) predicted longitudinal cognitive changes in patients with Alzheimer’s disease pathology.

In patients, both stepwise backward elimination and Bayesian model selection revealed an optimal predictive model that included both components of 18F-AV-1451 and the first (i.e. anterior temporal) component for 11C-PK11195. However, the MRI-derived atrophy component and demographic variables were excluded from the optimal predictive model of cognitive decline.

The researchers conclude that temporo-parietal tau pathology and anterior temporal neuroinflammation predict cognitive decline in patients with symptomatic Alzheimer’s disease pathology. This indicates the added value of PET biomarkers in predicting cognitive decline in Alzheimer’s disease, over and above MRI measures of brain atrophy and demographic data. The findings also support the strategy for targeting tau and neuroinflammation in disease-modifying therapy against Alzheimer’s disease.

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