Publication Type Academic Article
Authors Butler T, Wang X, Chiang G, Xi K, Niogi S, Glodzik L, Li Y, Razlighi Q, Zhou L, Hojjati S, Ozsahin I, Mao X, Maloney T, Tanzi E, Rahmouni N, Tissot C, Lussier F, Shah S, Shungu D, Gupta A, De Leon M, Mozley P, Pascoal T, Rosa-Neto P
Journal J Alzheimers Dis
Volume 99
Issue 1
Pagination 307-319
Date Published 01/01/2024
ISSN 1875-8908
Keywords Alzheimer Disease, Microglia, Aging, Brain Stem, Receptors, GABA, Positron-Emission Tomography
Abstract BACKGROUND: Alzheimer's disease (AD) pathology is considered to begin in the brainstem, and cerebral microglia are known to play a critical role in AD pathogenesis, yet little is known about brainstem microglia in AD. Translocator protein (TSPO) PET, sensitive to activated microglia, shows high signal in dorsal brainstem in humans, but the precise location and clinical correlates of this signal are unknown. OBJECTIVE: To define age and AD associations of brainstem TSPO PET signal in humans. METHODS: We applied new probabilistic maps of brainstem nuclei to quantify PET-measured TSPO expression over the whole brain including brainstem in 71 subjects (43 controls scanned using 11C-PK11195; 20 controls and 8 AD subjects scanned using 11C-PBR28). We focused on inferior colliculi (IC) because of visually-obvious high signal in this region, and potential relevance to auditory dysfunction in AD. We also assessed bilateral cortex. RESULTS: TSPO expression was normally high in IC and other brainstem regions. IC TSPO was decreased with aging (p = 0.001) and in AD subjects versus controls (p = 0.004). In cortex, TSPO expression was increased with aging (p = 0.030) and AD (p = 0.033). CONCLUSIONS: Decreased IC TSPO expression with aging and AD-an opposite pattern than in cortex-highlights underappreciated regional heterogeneity in microglia phenotype, and implicates IC in a biological explanation for strong links between hearing loss and AD. Unlike in cerebrum, where TSPO expression is considered pathological, activated microglia in IC and other brainstem nuclei may play a beneficial, homeostatic role. Additional study of brainstem microglia in aging and AD is needed.
DOI 10.3233/JAD-231312
PubMed ID 38669537
PubMed Central ID PMC11091576
Back to Top