Microglial activation protects against accumulation of tau aggregates in nondemented individuals with underlying Alzheimer’s disease pathology
Year: 2022
Type: article
Study design: Observational Study
Abstract: The role of microglia in tau accumulation is currently unclear but could provide an important insight into the mechanisms underlying Alzheimer’s disease (AD) 1 . Here, we measured the microglial marker soluble TREM2 and the disease-associated microglial activation stage 2 markers AXL, MERTK, GAS6, LPL, CST7, SPP1 and CSF1 in nondemented individuals from the Swedish BioFINDER-2 cohort who underwent longitudinal tau-positron emission tomography (PET), amyloid-PET and global cognitive assessment. To assess whether baseline microglial markers had an effect on AD-related changes, we studied three sub-groups of individuals: 121 with evidence of amyloid-PET pathology (A + ), 64 with additional evidence of tau-PET pathology (A + T + ) and 159 without amyloid- or tau-PET pathology (A − T − ). Our results showed that increased levels of TREM2 were associated with slower amyloid accumulation in A + individuals in addition to slower tau deposition and cognitive decline in A + T + subjects. Similarly, higher levels of AXL, MERTK, GAS6, LPL, CST7 and CSF1 predicted slower tau accumulation and/or cognitive decline in the A + T + group. These findings have important implications for future therapeutic strategies aiming to boost microglial protective functions in AD.
Source: Nature Aging
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $11,390
Funders: Alzheimer's Association, Alzheimer's Drug Discovery Foundation, Familjen Erling-Perssons Stiftelse, Stiftelsen för Gamla Tjänarinnor, EU Joint Programme – Neurodegenerative Disease Research, Australian Government, European Commission, Lunds Universitet, Hjärnfonden, Karolinska Institutet, Knut och Alice Wallenbergs Stiftelse, Vetenskapsrådet, Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse, Alzheimerfonden, Skånes universitetssjukhus, Marcus och Amalia Wallenbergs minnesfond, UK Dementia Research Institute, Demensfonden, Olav Thon Stiftelsen, Parkinsonfonden, H2020 European Research Council
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OpenAlex ID: W4310151228