The prognostic role of microglia and tau PET in Alzheimer’s disease

Abstract:

AbstractBackgroundNeuroinflammation is part of the pathophysiology of Alzheimer’s disease (AD), in addition to amyloid‐β plaques and tau neurofibrillary tangles. PET markers of microglial activation have indicated inflammation of temporo‐parietal regions, in proportion to disease severity. Here we test the prognostic value of [11C]PK11195 PET on longitudinal clinical decline in AD, alone and in combination with MRI and tau ([18F]AV‐1451) PET imaging.MethodTwenty‐six patients with Alzheimer’s dementia or amyloid‐positive Mild Cognitive Impairment, and 29 controls underwent multi‐modal assessment with [11C]PK11195 PET, [18F]AV‐1451 PET, structural MRI, and annual cognitively assessment with the Revised Addenbrooke's Cognitive Examination. Regional PET binding potentials and grey‐matter volumes from fifteen bilateral temporo‐parietal region were summarised by method‐specific Principal Component Analyses (PCAs). The rate of longitudinal cognitive decline was estimated using a Latent Growth Curve Model. The predictive value of PET and MRI on cognitive decline was tested with modality‐specific regression models, and a multi‐modality regression model.ResultPCA on each PET ligand consistently identified one component in anterior temporal regions, and another in posterior temporo‐parietal regions, while for MRI, a single component was identified across all regions. Worse annual rate of cognitive decline correlated with higher [11C]PK11195 in the anterior temporal component (r = −0.47, p = 0.002), and in posterior temporo‐parietal regions (r = −0.39, p = 0.012). An optimal multi‐modality model was identified by stepwise regression and Bayesian selection, that included the anterior [11C]PK11195 component and both [18F]AV‐1451 components as predictors of cognitive decline (R2 = 0.418; p = 0.001), but not their interaction and not the baseline MRI.ConclusionThese results suggest that in addition to tau pathology, microglial activation in the anterior temporal lobe plays a key role in predicting future cognitive decline in patients with AD. The results support therapeutic strategies targeting tau and microglial activation as disease‐modifying therapy against AD.