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

• Published in: Molecular neurodegeneration Vol. 13; no. 1; pp. 66 - 16
• Main Authors: Gratuze, Maud, Leyns, Cheryl E. G., Holtzman, David M.
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 20.12.2018; BioMed Central; BMC
• Subjects: Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Animal models; Animals; ApoE; Apolipoproteins; Dementia; Dementia disorders; Disease Models, Animal; Genetic factors; Genomes; Gliosis; Health risk assessment; Heritability; Humans; Immune system; Life Sciences; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Microglia; Microglia - metabolism; Myeloid cells; Neurodegeneration; Neurofibrillary tangles; Neuropathology; Pathogenesis; Peptides; Plaque, Amyloid - pathology; Proteins; Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; Review; Senile plaques; Tau protein; TREM2; β-Amyloid; ApoE; TREM2; Gliosis; Alzheimer’s disease; Neurodegeneration; Microglia
• ISSN: 1750-1326; 1750-1326
• DOI: 10.1186/s13024-018-0298-9

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 neurofibrillary tangles of aggregated, abnormally hyperphosphorylated tau protein. The majority of AD cases are late-onset, after the age of 65, where a clear cause is still unknown. However, there are likely different multifactorial contributors including age, enviornment, biology and genetics which can increase risk for the disease. Genetic predisposition is considerable, with heritability estimates of 60-80%. Genetic factors such as rare variants of TREM2 (triggering receptor expressed on myeloid cells-2) strongly increase the risk of developing AD, confirming the role of microglia in AD pathogenesis. In the last 5 years, several studies have dissected the mechanisms by which TREM2, as well as its rare variants affect amyloid and tau pathologies and their consequences in both animal models and in human studies. In this review, we summarize increases in our understanding of the involvement of TREM2 and microglia in AD development that may open new therapeutic strategies targeting the immune system to influence AD pathogenesis.