Gray matter changes related to microglial activation in Alzheimer's disease

NEUROBIOLOGY OF AGING

卷:94

Article

Nicastro, Nicolas^1,2  Malpetti, Maura³  Mak, Elijah¹  Williams, Guy B.⁴  Bevan-Jones, W. Richard³  Carter, Stephen F.¹  Passamonti, Luca^3,5  Fryer, Tim D.^3,4  Hong, Young T.^3,4  Aigbirhio, Franklin, I⁴  Rowe, James B.^3,6  O'Brien, John T.¹ 

[1] Univ Cambridge, Dept Psychiat, Cambridge, England

[2] Geneva Univ Hosp, Dept Clin Neurosci, Geneva, Switzerland

[3] Univ Cambridge, Dept Clin Neurosci, Cambridge, England

[4] Cognit Univ Cambridge, Wolfson Brain Imaging Ctr, Cambridge, England

[5] CNR, Ist Bioimmagini & Fisiol Mol IBFM, Milan, Italy

[6] MRC, Cognit & Brain Sci Unit, Cambridge, England

关键词: Alzheimer's disease;    Neuroinflammation;    PET;    Grey matter;    Atrophy;    Cortical thickness;    MRI;   

DOI  :  10.1016/j.neurobiolaging.2020.06.010

来源: Elsevier

【 摘 要 】

Neuroinflammation is increasingly recognized as playing a key pathogenetic role in Alzheimer's disease (AD). We examined the relationship between in vivo neuroinflammation and gray matter (GM) changes. Twenty-eight subjects with clinically probable AD (n = 14) and amyloid-positive mild cognitive impairment (n = 14) (age 71.9 +/- 8.4 years, 46% female) and 24 healthy controls underwent structural 3T brain MRI. AD/mild cognitive impairment participants exhibited GM atrophy and cortical thinning in AD-related temporoparietal regions (false discovery rateecorrected p < 0.05). Patients also showed increased microglial activation in temporal cortices. Higher C-11-PK11195 binding in these regions was associated with reduced volume and cortical thickness in parietal, occipital, and cingulate areas (false discovery rate p < 0.05). Hippocampal GM atrophy and parahippocampal cortical thinning were related to worse cognition (p < 0.05), but these effects were not mediated by microglial activation. This study demonstrates an association between in vivo microglial activation and markers of GM damage in AD, positioning neuroinflammation as a potential target for immunotherapeutic strategies. (C) 2020 The Author(s). Published by Elsevier Inc.

【 授权许可】

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