Microglial responses partially mediate the effect of Aβ on cognition in Alzheimer's disease

TY - JOUR

T1 - Microglial responses partially mediate the effect of Aβ on cognition in Alzheimer's disease

AU - Madsen, Lasse S

AU - Ismail, Rola

AU - Parbo, Peter

AU - Kjeldsen, Pernille L

AU - Schaldemose, Jeppe L

AU - Hansen, Kim V

AU - Gottrup, Hanne

AU - Aanerud, Joel

AU - Eskildsen, Simon F

AU - Brooks, David J

PY - 2024/11

Y1 - 2024/11

N2 - INTRODUCTION: Microglial responses are an integral part of Alzheimer's disease (AD) pathology and are associated with amyloid beta (Aβ) deposition. This study aimed to investigate the effects of Aβ and microglial responses on global cognitive impairment.METHODS: In this longitudinal study, 28 patients with mild cognitive impairment and 11 healthy controls underwent 11C-PK11195 and 11C-Pittsburgh compound B positron emission tomography (PET), structural magnetic resonance imaging scans, and global cognitive ratings at baseline and 2-year follow-up. Correlations between PET uptake and global cognition were assessed. Additionally, the mediation effect of the microglial response on the association between Aβ load and global cognition was assessed. RESULTS: Aβ load and the microglial response were both independently detrimental to global cognitive performance at baseline; however, at 2-year follow-up the association between Aβ load and global cognitive ratings was partially mediated by the microglial response.DISCUSSION: As AD progresses, the associated microglial response partially mediates the detrimental effect of aggregated Aβ on cognition.HIGHLIGHTS: This was a longitudinal study of amyloid beta (Aβ), microglial responses, and global cognitive performance. Aβ and microglial responses both affect cognition in early Alzheimer's disease. Microglial response partially mediates the effect of Aβ on cognition in later stages.

AB - INTRODUCTION: Microglial responses are an integral part of Alzheimer's disease (AD) pathology and are associated with amyloid beta (Aβ) deposition. This study aimed to investigate the effects of Aβ and microglial responses on global cognitive impairment.METHODS: In this longitudinal study, 28 patients with mild cognitive impairment and 11 healthy controls underwent 11C-PK11195 and 11C-Pittsburgh compound B positron emission tomography (PET), structural magnetic resonance imaging scans, and global cognitive ratings at baseline and 2-year follow-up. Correlations between PET uptake and global cognition were assessed. Additionally, the mediation effect of the microglial response on the association between Aβ load and global cognition was assessed. RESULTS: Aβ load and the microglial response were both independently detrimental to global cognitive performance at baseline; however, at 2-year follow-up the association between Aβ load and global cognitive ratings was partially mediated by the microglial response.DISCUSSION: As AD progresses, the associated microglial response partially mediates the detrimental effect of aggregated Aβ on cognition.HIGHLIGHTS: This was a longitudinal study of amyloid beta (Aβ), microglial responses, and global cognitive performance. Aβ and microglial responses both affect cognition in early Alzheimer's disease. Microglial response partially mediates the effect of Aβ on cognition in later stages.

KW - Alzheimer's disease

KW - PK11195

KW - amyloid beta

KW - cognition

KW - mild cognitive impairment

KW - position emission tomography

KW - translocator protein

UR - http://www.scopus.com/inward/record.url?scp=85205963623&partnerID=8YFLogxK

U2 - 10.1002/alz.14298

DO - 10.1002/alz.14298

M3 - Journal article

C2 - 39392185

SN - 1552-5260

VL - 20

SP - 8028

EP - 8037

JO - Alzheimer's & Dementia

JF - Alzheimer's & Dementia

IS - 11

ER -