RESUMO
INTRODUCTION: Evidence suggests microglial activation precedes regional tau and neurodegeneration in Alzheimer's disease (AD). We characterized microglia with translocator protein (TSPO) positron emission tomography (PET) within an AD progression model where global amyloid beta (Aß) precedes local tau and neurodegeneration, resulting in cognitive impairment. METHODS: Florbetaben, PBR28, and MK-6240 PET, T1 magnetic resonance imaging, and cognitive measures were performed in 19 cognitively unimpaired older adults and 22 patients with mild cognitive impairment or mild AD to examine associations among microglia activation, Aß, tau, and cognition, adjusting for neurodegeneration. Mediation analyses evaluated the possible role of microglial activation along the AD progression model. RESULTS: Higher PBR28 uptake was associated with higher Aß, higher tau, and lower MMSE score, independent of neurodegeneration. PBR28 mediated associations between tau in early and middle Braak stages, between tau and neurodegeneration, and between neurodegeneration and cognition. DISCUSSION: Microglia are associated with AD pathology and cognition and may mediate relationships between subsequent steps in AD progression.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Idoso , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Microglia/metabolismo , Proteínas tau/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Disfunção Cognitiva/metabolismo , Progressão da Doença , Receptores de GABA/metabolismoRESUMO
Autopsy and imaging studies have demonstrated a typical pattern of tau progression in Alzheimer's disease (AD), spreading to previously unaffected regions in an anatomical sequence of 'Braak' stages. In a recent study, Pascoal et al. provide evidence that microgliosis colocalizes with tau in a Braak-like pattern, furthering the notion that microglial activation is strongly related to the propagation of tangle pathology.
