Tau and Ab imaging, CSF measures, and cognition in Alzheimer's disease

Abstract

Alzheimer's disease (AD) is characterized by two molecular pathologies: cerebral b-Amyloidosis in the form of b-Amyloid (Ab) plaques and tauopathy in the form of neurofibrillary tangles, neuritic plaques, and neuropil threads. Until recently, only Ab could be studied in humans using positron emission tomography (PET) imaging owing to a lack of tau PET imaging agents. Clinical pathological studies have linked tau pathology closely to the onset and progression of cognitive symptoms in patients with AD. We report PET imaging of tau and Ab in a cohort of cognitively normal older adults and those with mild AD. Multivariate analyses identified unique disease-related stereotypical spatial patterns (topographies) for deposition of tau and Ab. These PET imaging tau and Ab topographies were spatially distinct but correlated with disease progression. Cerebrospinal fluid measures of tau, often used to stage preclinical AD, correlated with tau deposition in the temporal lobe. Tau deposition in the temporal lobe more closely tracked dementia status and was a better predictor of cognitive performance than Ab deposition in any region of the brain. These data support models of AD where tau pathology closely tracks changes in brain function that are responsible for the onset of early symptoms in AD.