Serum Soluble Triggering Receptor Expressed on Myeloid Cells 2 as a Biomarker for Incident Dementia: The Hisayama Study

Ohara, Tomoyuki; Hata, Jun; Tanaka, Masashi; Honda, Takanori; Yamakage, Hajime; Yoshida, Daigo; Inoue, Takayuki; Hirakawa, Yoichiro; Kusakabe, Toru; Shibata, Mao; Teraoka, T.; Kitazono, Takanari; Kanba, Shigenobu; Satoh‐Asahara, Noriko; Ninomiya, Toshiharu

doi:10.1002/ana.25385

Cited by 52 publications

(78 citation statements)

References 46 publications

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“…Extensive blood measurements of sTREM2 have rarely been performed; in the few studies involving these measurements, differences based on AD diagnosis were not evident, and whether there was a correlation with CSF sTREM2 levels was unclear 73 . A recent longitudinal follow-up study in Japan demonstrated that high serum sTREM2 levels were associated with future overall development of dementia, rather than AD or vascular dementia 74 . Additional studies with more refined measurement tools are needed to elucidate the precise value of blood sTREM2 levels as a biomarker for AD.…”

Section: Soluble Triggering Receptor Expressed On Myeloid Cells 2 (Stmentioning

confidence: 99%

New fluid biomarkers tracking non-amyloid-β and non-tau pathology in Alzheimer’s disease

2020

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Cerebrospinal fluid (CSF) biomarkers based on the core pathological proteins associated with Alzheimer's disease (AD), i.e., amyloid-β (Aβ) and tau protein, are widely regarded as useful diagnostic biomarkers. However, a lack of biomarkers for monitoring the treatment response and indexing clinical severity has proven to be problematic in drug trials targeting Aβ. Therefore, new biomarkers are needed to track non-Aβ and non-tau pathology. Many proteins involved in the pathophysiological progression of AD have shown promise as new biomarkers. Neurodegeneration-and synapse-related biomarkers in CSF (e.g., neurofilament light polypeptide [NFL], neurogranin, and visinin-like protein 1) and blood (e.g., NFL) aid prediction of AD progress, as well as early diagnosis. Neuroinflammation, lipid dysmetabolism, and impaired protein clearance are considered important components of AD pathophysiology. Inflammation-related proteins in the CSF, such as progranulin, intercellular adhesion molecule 1, and chitinase-3-like protein 1 (YKL-40), are useful for the early detection of AD and can represent clinical severity. Several lipid metabolism-associated biomarkers and protein clearance-linked markers have also been suggested as candidate AD biomarkers. Combinations of subsets of new biomarkers enhance their utility in terms of broadly characterizing AD-associated pathological changes, thereby facilitating precise selection of susceptible patients and comprehensive monitoring of the treatment response. This approach could facilitate the development of effective treatments for AD.

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Section: Soluble Triggering Receptor Expressed On Myeloid Cells 2 (Stmentioning

confidence: 99%

New fluid biomarkers tracking non-amyloid-β and non-tau pathology in Alzheimer’s disease

2020

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“…novel marker for cognitive impairment in Japanese patients with nonobese type 2 diabetes (22) and in the general elderly Japanese population (23). However, the pathophysiological significance of TREM2 in CAA and the effects of taxifolin on microglial phenotypes have not been clarified.…”

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confidence: 99%

Pleiotropic neuroprotective effects of taxifolin in cerebral amyloid angiopathy

Inoue

Saitô

Tanaka

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Cerebral amyloid angiopathy (CAA) results from amyloid-β deposition in the cerebrovasculature. It is frequently accompanied by Alzheimer's disease and causes dementia. We recently demonstrated that in a mouse model of CAA, taxifolin improved cerebral blood flow, promoted amyloid-β removal from the brain, and prevented cognitive dysfunction when administered orally. Here we showed that taxifolin inhibited the intracerebral production of amyloid-β through suppressing the ApoE-ERK1/2-amyloid-β precursor protein axis, despite the low permeability of the bloodbrain barrier to taxifolin. Higher expression levels of triggering receptor expressed on myeloid cell 2 (TREM2) were associated with the exacerbation of inflammation in the brain. Taxifolin suppressed inflammation, alleviating the accumulation of TREM2expressing cells in the brain. It also mitigated glutamate levels and oxidative tissue damage and reduced brain levels of active caspases, indicative of apoptotic cell death. Thus, the oral administration of taxifolin had intracerebral pleiotropic neuroprotective effects on CAA through suppressing amyloid-β production and beneficially modulating proinflammatory microglial phenotypes.cerebral amyloid angiopathy | neuroprotection | taxifolin | triggering receptor expressed on myeloid cell 2

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“…Follow-up studies with longitudinal sampling may reduce the variance observed. For example, in a prospective longitudinal study, higher levels of sTREM2 in blood were associated with increased risk of developing dementia, AD, and vascular dementia in the general elderly Japanese population (Ohara et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

CSF sTREM2 correlates with CSF tau in advancing Parkinson’s disease

Wilson

Swarovski

Linortner

et al. 2019

Preprint

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222 Introduction: 565 Participants and Methods: 966 Abstract Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease (AD) and affects 1% of the population above 60 years old. Although PD commonly manifests with motor symptoms, a majority of patients with PD subsequently develop cognitive impairment which often progresses to dementia, a major cause of morbidity and disability. PD is characterized by α -synuclein accumulation that frequently associates with amyloid beta (Aβ) and tau fibrils, the hallmarks of AD neuropathologic changes; this cooccurrence suggests that onset of cognitive decline in PD may be associated with appearance of pathologic Aβ and/or tau. Recent studies have highlighted the appearance of the soluble form of the Triggering Receptor Expressed on Myeloid cells 2 (sTREM2) receptor in CSF during development of AD. Given the known association of microglial activation with advancing PD, we investigated whether CSF and/or plasma sTREM2 increased with progression to PD dementia. We examined 165 participants consisting of 17 cognitively normal elderly, 45 PD patients with no cognitive impairment, 86 with mild cognitive impairment, and 17 with dementia. Stratification of subjects by CSF Aβ and tau levels revealed that CSF sTREM2concentrations were elevated in PD subgroups with abnormal tau, but not Aβ, CSF concentration. These findings indicate that CSF sTREM2 could serve as a surrogate immune biomarker of neuronal injury in PD that is associated with cognitive decline.

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Serum Soluble Triggering Receptor Expressed on Myeloid Cells 2 as a Biomarker for Incident Dementia: The Hisayama Study

Cited by 52 publications

References 46 publications

New fluid biomarkers tracking non-amyloid-β and non-tau pathology in Alzheimer’s disease

New fluid biomarkers tracking non-amyloid-β and non-tau pathology in Alzheimer’s disease

Pleiotropic neuroprotective effects of taxifolin in cerebral amyloid angiopathy

CSF sTREM2 correlates with CSF tau in advancing Parkinson’s disease

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