A Computational Approach in the Systematic Search of the Interaction Partners of Alternatively Spliced TREM2 Isoforms.

Alzheimer's disease is the most common form of dementia, characterized by the pathological accumulation of amyloid-beta (Aβ) plaques and tau neurofibrillary tangles. Triggering receptor expressed on myeloid cells 2 (TREM2) is increasingly recognized as playing a central role in Aβ clearance and microglia activation in AD. The gene transcriptional product is alternatively spliced to produce three different protein isoforms.

ATN cerebrospinal fluid biomarkers in dementia with Lewy bodies: Initial results from the United States Dementia with Lewy Bodies Consortium.

Introduction: The National Institute on Aging - Alzheimer's Association (NIA-AA) ATN research framework proposes to use biomarkers for amyloid (A), tau (T), and neurodegeneration (N) to stage individuals with AD pathological features and track changes longitudinally. The overall aim was to utilize this framework to characterize pre-mortem ATN status longitudinally in a clinically diagnosed cohort of dementia with Lewy bodies (DLB) and to correlate it with the post mortem diagnosis.

Methods: The cohort was subtyped by cerebrospinal fluid (CSF) ATN category.

TREM2 alters the phagocytic, apoptotic and inflammatory response to Aβ in HMC3 cells.

Alzheimer's disease (AD) is characterized by the accumulation in the brain of extracellular amyloid β (Aβ) plaques as well as intraneuronal inclusions (neurofibrillary tangles) consisting of total tau and phosphorylated tau. Also present are dystrophic neurites, loss of synapses, neuronal death, and gliosis. AD genetic studies have highlighted the importance of inflammation in this disease by identifying several risk associated immune response genes, including TREM2.

Genetically enhancing the expression of chemokine domain of CXCL1 fails to prevent tau pathology in mouse models of tauopathy.

Background: Fractalkine (CXCL1) and its receptor (CXCR1) play an important role in regulating microglial function. We have previously shown that Cxcr1 deficiency exacerbated tau pathology and led to cognitive impairment. However, it is still unclear if the chemokine domain of the ligand CXCL1 is essential in regulating neuronal tau pathology.

Regulation of ADAM10 by miR-140-5p and potential relevance for Alzheimer's disease.

Recent reports in Alzheimer's disease (AD) research suggest that alterations in microRNA (miRNA) expression are associated with disease pathology. Our previous studies suggest that A Disintegrin and Metalloproteinase 10 (ADAM10) expression is important in AD and could be modulated by an extended regulatory region that includes the 3' untranslated region. In this study, we have investigated the role of trans-acting factors in ADAM10 gene regulation.

TREM2 deficiency exacerbates tau pathology through dysregulated kinase signaling in a mouse model of tauopathy.

Background: Genetic variants of the Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) confer increased risk of developing late-onset Alzheimer's Disease (LOAD) and other neurodegenerative disorders. Recent studies provided insight into the multifaceted roles of TREM2 in regulating extracellular β-amyloid (Aβ) pathology, myeloid cell accumulation, and inflammation observed in AD, yet little is known regarding the role of TREM2 in regulating intracellular microtubule associated protein tau (MAPT; tau) pathology in neurodegenerative diseases and in AD, in particular.

Results: Here we report that TREM2 deficiency leads to accelerated and exacerbated hyperphosphorylation and aggregation of tau in a humanized mouse model of tauopathy.