Association of β-Amyloid, Microglial Activation, Cortical Thickness, and Metabolism in Older Adults Without Dementia.

Background And Objectives: Plasma β-amyloid (Aβ)/Aβ levels have shown promise in identifying Aβ-PET positive individuals. This study explored the concordance and discordance of plasma Aβ/Aβ positivity (Plasma±) with CSF Aβ/Aβ positivity (CSF±) and Aβ-PET positivity (PET±) in older adults without dementia. Associations of Aβ deposition, cortical thickness, glucose metabolism, and microglial activation were also investigated.

TREM2 receptor protects against complement-mediated synaptic loss by binding to complement C1q during neurodegeneration.

Triggering receptor expressed on myeloid cells 2 (TREM2) is strongly linked to Alzheimer's disease (AD) risk, but its functions are not fully understood. Here, we found that TREM2 specifically attenuated the activation of classical complement cascade via high-affinity binding to its initiator C1q. In the human AD brains, the formation of TREM2-C1q complexes was detected, and the increased density of the complexes was associated with lower deposition of C3 but higher amounts of synaptic proteins.

Identification of the minimal active soluble TREM2 sequence for modulating microglial phenotypes and amyloid pathology.

Background: TREM2 is a microglial receptor genetically linked to the risk for Alzheimer's disease (AD). The cerebrospinal fluid (CSF) levels of soluble TREM2 (sTREM2) have emerged as a valuable biomarker for the disease progression in AD and higher CSF levels of sTREM2 are linked to slower cognitive decline. Increasing sTREM2 in mouse models of amyloidosis reduces amyloid-related pathology through modulating microglial functions, suggesting a beneficial role of sTREM2 in microglia biology and AD pathology.