The multiplex model of the genetics of Alzheimer's disease

R Sims, M Hill, J Williams - Nature neuroscience, 2020 - nature.com
Genes play a strong role in Alzheimer's disease (AD), with late-onset AD showing heritability
of 58–79% and early-onset AD showing over 90%. Genetic association provides a robust …

New insights into the role of TREM2 in Alzheimer's disease

M Gratuze, CEG Leyns, DM Holtzman - Molecular neurodegeneration, 2018 - Springer
Alzheimer's disease (AD) is the leading cause of dementia. The two histopathological
markers of AD are amyloid plaques composed of the amyloid-β (Aβ) peptide, and …

Meningeal lymphatics affect microglia responses and anti-Aβ immunotherapy

S Da Mesquita, Z Papadopoulos, T Dykstra, L Brase… - Nature, 2021 - nature.com
Alzheimer's disease (AD) is the most prevalent cause of dementia. Although there is no
effective treatment for AD, passive immunotherapy with monoclonal antibodies against …

Genomic atlas of the proteome from brain, CSF and plasma prioritizes proteins implicated in neurological disorders

C Yang, FHG Farias, L Ibanez, A Suhy, B Sadler… - Nature …, 2021 - nature.com
Understanding the tissue-specific genetic controls of protein levels is essential to uncover
mechanisms of post-transcriptional gene regulation. In this study, we generated a genomic …

Tau activates microglia via the PQBP1-cGAS-STING pathway to promote brain inflammation

M **, H Shiwaku, H Tanaka, T Obita, S Ohuchi… - Nature …, 2021 - nature.com
Brain inflammation generally accompanies and accelerates neurodegeneration. Here we
report a microglial mechanism in which polyglutamine binding protein 1 (PQBP1) senses …

[HTML][HTML] Trem2 restrains the enhancement of tau accumulation and neurodegeneration by β-amyloid pathology

SH Lee, WJ Meilandt, L **e, VD Gandham, H Ngu… - Neuron, 2021 - cell.com
Loss-of-function TREM2 mutations strongly increase Alzheimer's disease (AD) risk. Trem2
deletion has revealed protective Trem2 functions in preclinical models of β-amyloidosis, a …

Chi3l1/YKL-40 is controlled by the astrocyte circadian clock and regulates neuroinflammation and Alzheimer's disease pathogenesis

BV Lananna, CA McKee, MW King… - Science translational …, 2020 - science.org
Regulation of glial activation and neuroinflammation are critical factors in the pathogenesis
of Alzheimer's disease (AD). YKL-40, a primarily astrocytic protein encoded by the gene …

TREM2 function impedes tau seeding in neuritic plaques

CEG Leyns, M Gratuze, S Narasimhan, N Jain… - Nature …, 2019 - nature.com
Variants in the triggering receptor expressed on myeloid cells 2 (TREM2) have been
associated with increased risk for sporadic, late-onset Alzheimer's disease. Here we show …

[HTML][HTML] TREM2 ectodomain and its soluble form in Alzheimer's disease

J Yang, Z Fu, X Zhang, M **ong, L Meng… - Journal of …, 2020 - Springer
Triggering receptor expressed on myeloid cells 2 (TREM2) is a receptor mainly expressed
on the surface of microglia. It mediates multiple pathophysiological processes in various …

[HTML][HTML] Alzheimer risk-increasing TREM2 variant causes aberrant cortical synapse density and promotes network hyperexcitability in mouse models

M Das, W Mao, Y Voskobiynyk, D Necula, I Lew… - Neurobiology of …, 2023 - Elsevier
The R47H variant of triggering receptor expressed on myeloid cells 2 (TREM2) increases
the risk of Alzheimer's disease (AD). To investigate potential mechanisms, we analyzed …