Journal Article (Review Article)

DZNE-2023-01022

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Stimulation of TREM2 with agonistic antibodies-an emerging therapeutic option for Alzheimer's disease.

Schlepckow, K. (First author)DZNE* ; Morenas Rodriguez, E.Extern* ; Hong, S. ; Haass, C. (Last author)DZNE*

2023
Lancet Publ. Group London

This record in other databases:    

Please use a persistent id in citations: doi:10.1016/S1474-4422(23)00247-8

Abstract: Neurodegenerative disorders, including Alzheimer's disease, are associated with microgliosis. Microglia have long been considered to have detrimental roles in Alzheimer's disease. However, functional analyses of genes encoding risk factors that are linked to late-onset Alzheimer's disease, and that are enriched or exclusively expressed in microglia, have revealed unexpected protective functions. One of the major risk genes for Alzheimer's disease is TREM2. Risk variants of TREM2 are loss-of-function mutations affecting chemotaxis, phagocytosis, lipid and energy metabolism, and survival and proliferation. Agonistic anti-TREM2 antibodies have been developed to boost these protective functions in patients with intact TREM2 alleles. Several anti-TREM2 antibodies are in early clinical trials, and current efforts aim to achieve more efficient transport of these antibodies across the blood-brain barrier. PET imaging could be used to monitor target engagement. Data from animal models, and biomarker studies in patients, further support a rationale for boosting TREM2 functions during the preclinical stage of Alzheimer's disease.

Keyword(s): Animals (MeSH) ; Humans (MeSH) ; Alzheimer Disease: genetics (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; Microglia: metabolism (MeSH) ; Mutation (MeSH) ; Antibodies: genetics (MeSH) ; Antibodies: metabolism (MeSH) ; Disease Models, Animal (MeSH) ; Membrane Glycoproteins: genetics (MeSH) ; Receptors, Immunologic: genetics (MeSH) ; Antibodies ; TREM2 protein, human ; Membrane Glycoproteins ; Receptors, Immunologic

---

Contributing Institute(s):

1. Molecular Neurodegeneration (AG Haass)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2023

---

Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 40 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---