Higher Peripheral TREM2 mRNA Levels Relate to Cognitive Deficits and Hippocampal Atrophy in Alzheimer's Disease and Amnestic Mild Cognitive Impairment.

  title={Higher Peripheral TREM2 mRNA Levels Relate to Cognitive Deficits and Hippocampal Atrophy in Alzheimer's Disease and Amnestic Mild Cognitive Impairment.},
  author={Yi Jayne Tan and Adeline Su Lyn Ng and Ashwati Vipin and Joseph K. W. Lim and Russell J Chander and Fang Ji and Ying-wei Qiu and Simon Kang Seng Ting and Shahul Hameed and Tih-Shih Lee and Li Zeng and Nagaendran Kandiah and Juan Helen Zhou},
  journal={Journal of Alzheimer's disease : JAD},
  volume={58 2},
BACKGROUND Variants in triggering receptor expressed on myeloid cells 2 (TREM2) are associated with increased Alzheimer's disease (AD) risk. Recent studies have reported inconsistent peripheral TREM2 mRNA expression levels and relationship with cognitive scores in AD and mild cognitive impairment (MCI). Additionally, no study has examined the association of peripheral TREM2 levels with neuroimaging measures in AD and MCI. OBJECTIVE To determine peripheral TREM2 mRNA levels in AD, amnestic MCI… 

Figures and Tables from this paper


TREM2 may be useful as an early peripheral biomarker for the development of AD and it is speculated that TREM2 and ApoE ε4 may interact synergistically in the preclinical stage of AD.

Peripheral TREM2 mRNA levels in early and late-onset Alzheimer disease’s patients

Examination of expression levels of TREM2 mRNA in peripheral leukocytes of early and late-onset AD patients and the effect of the presence of APOE ε4 allele can suggest that age is a factor that increases TREM1 expression, and TREM 2 and APOEε4 may interact together in the pathogenesis of LOAD.

APOE4 and Confluent White Matter Hyperintensities Have a Synergistic Effect on Episodic Memory Impairment in Prodromal Dementia.

Clinicians targeting WMH would need to consider the APOE4 allele and WMH severity status to strategize cognitive interventions as well as the role of confluent and non-confluent WMH on cognition.

Regional White Matter Hyperintensity Influences Grey Matter Atrophy in Mild Cognitive Impairment.

Although WMH volume was highest in AD subjects, it had a more pervasive influence on brain structure and cognitive impairment in MCI, highlighting the importance of early detection of cerebrovascular disease, as its intervention at the MCI stage might potentially slow down neurodegeneration.

Untangling the Role of TREM2 in Conjugation with Microglia in Neuronal Dysfunction: A Hypothesis on a Novel Pathway in the Pathophysiology of Alzheimer's Disease.

It is indicated that TREM2 has the potential to ameliorate the Aβ burden, though with differential clearance ability and may act as a potential therapeutic target.

TREM2 expression in the human brain: a marker of monocyte recruitment?

Observations, using the HPA010917 anti‐TREM2 antibody, suggest that TREM2 is not expressed by microglia but instead seems to be a marker of recruited monocytes in the human brain, emphasizing the importance of systemic immune responses in the development and progression of Alzheimer's disease.

Inflammation as a central mechanism in Alzheimer's disease

Association Between sTREM2, an Immune Biomarker of Microglial Activation, and Aging-Related Brain Volume Changes in Community-Dwelling Older Adults: A 7-Year Follow-Up Study

Serum sTREM2 level could not serve as an immune biomarker of aging-related volume changes in brain regions closely related to cognitive function in older adults aged 65 years and above.

Distinct network topology in Alzheimer’s disease and behavioral variant frontotemporal dementia

These findings underscore the reciprocal relationships between the default, control, and salience networks that may account for the cognitive decline and neuropsychiatric symptoms in dementia.



Increased expression of TREM2 in peripheral blood of Alzheimer's disease patients.

According to ROC curve analysis, the diagnostic accuracy for TREM2 protein levels on monocytes was 70%, with the sensitivity and specificity 68% and 72%, respectively, indicating that T REM2 might serve as a novel noninvasive biomarker for AD diagnosis.

Apolipoprotein E ε4 is associated with disease-specific effects on brain atrophy in Alzheimer's disease and frontotemporal dementia

The influence of ε4 allele carrier status on the pattern of gray matter atrophy and disease severity in 51 patients with probable AD and 31 patients with behavioral variant frontotemporal dementia (bvFTD), compared with 56 healthy controls was investigated.

TREM2 mRNA Expression in Leukocytes Is Increased in Alzheimer’s Disease and Schizophrenia

TREM2 expression in leukocytes is elevated not only in AD but also in schizophrenia, as observed in neurocognitive disorders such as AD and schizophrenia.

TREM2 Protein Expression Changes Correlate with Alzheimer's Disease Neurodegenerative Pathologies in Post‐Mortem Temporal Cortices

Increased expression of TREM2 protein was found to significantly correlate with increases of phosphorylated‐tau and active caspase 3, a marker of apoptosis, and also loss of the presynaptic protein SNAP25.

TREM2 upregulation correlates with 5-hydroxymethycytosine enrichment in Alzheimer’s disease hippocampus

DNA methylation, and particularly 5hmC, may be involved in regulating TREM2 mRNA expression in the AD brain and further studies are guaranteed to investigate in depth the role of5hmC in AD and other neurodegenerative disorders.

Cognition, brain atrophy, and cerebrospinal fluid biomarkers changes from preclinical to dementia stage of Alzheimer's disease and the influence of apolipoprotein e.

EF/PS decline and right parietal atrophy might act as non-invasive screening tests for abnormal amyloid deposition in cognitively normal elderly and APOE modulation on subsequent trajectories in cognition and atrophy should be taken into account when analyzing disease progression.

TREM2 variants in Alzheimer's disease.

Heterozygous rare variants in TREM2 are associated with a significant increase in the risk of Alzheimer's disease.

Mild cognitive impairment: clinical characterization and outcome.

Patients who meet the criteria for MCI can be differentiated from healthy control subjects and those with very mild AD, and appear to constitute a clinical entity that can be characterized for treatment interventions.

Longitudinal changes in cognition and behavior in asymptomatic carriers of the APOE e4 allele

Memory declined in APOE e4 carriers before the symptomatic presentation of MCI in a cohort whose mean age was 60 years over a median period of 33 months, and began prior to age 60.