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CSF sTREM2 and Tau Work Together in Predicting Increased Temporal Lobe Atrophy in Older Adults
Nathalie Bodd Halaas1,2,3, Kristi Henjum1,3,4, Kaj Blennow5
1Oslo Delirium Research Group, Department of Geriatric Medicine, Oslo University Hospital, 0424 Oslo, Norway.
Abstract:
Neuroinflammation may be a key factor in brain atrophy in aging and age-related neurodegenerative disease. The objective of this study was to test the association between microglial expression of soluble Triggering Receptor Expressed on Myeloid Cells 2 (sTREM2), as a measure of neuroinflammation, and brain atrophy in cognitively unimpaired older adults. Brain magnetic resonance imagings (MRIs) and cerebrospinal fluid (CSF) sTREM2, total tau (t-tau), phosphorylated181 tau (p-tau), and Aβ42 were analyzed in 115 cognitively unimpaired older adults, classified according to the A/T/(N)-framework. MRIs were repeated after 2 (n = 95) and 4 (n = 62) years. High baseline sTREM2 was associated with accelerated cortical thinning in the temporal cortex of the left hemisphere, as well as bilateral hippocampal atrophy, independently of age, Aβ42, and tau. sTREM2-related atrophy only marginally increased with biomarker positivity across the AD continuum (A-T- #x2292; A+T- #x2292; A+T+) but was significantly stronger in participants with a high level of p-tau (T+). sTREM2-related cortical thinning correlated significantly with areas of high microglial-specific gene expression in the Allen Human Brain Atlas. In conclusion, increased CSF sTREM2 was associated with accelerated cortical and hippocampal atrophy in cognitively unimpaired older participants, particularly in individuals with tau pathology. This suggests a link between neuroinflammation, neurodegeneration, and amyloid-independent tauopathy.
Insights
High levels of soluble Triggering Receptor Expressed on Myeloid Cells 2 (sTREM2), a marker of neuroinflammation, are linked to accelerated brain atrophy in cognitively healthy older adults, especially those with tau pathology.
Area of Science:
- Neuroscience
- Neuroimmunology
- Aging Research
Background:
- Neuroinflammation is implicated in brain atrophy during aging and neurodegenerative diseases.
- Soluble Triggering Receptor Expressed on Myeloid Cells 2 (sTREM2) serves as a biomarker for microglial activation and neuroinflammation.
Purpose of the Study:
- To investigate the association between CSF sTREM2 levels and brain atrophy in cognitively unimpaired older adults.
- To explore the relationship between sTREM2, neuroinflammation, and neurodegenerative markers like tau and amyloid-beta.
Main Methods:
- Analysis of brain MRIs and cerebrospinal fluid (CSF) biomarkers (sTREM2, t-tau, p-tau, Aβ42) in 115 cognitively unimpaired older adults.
- Longitudinal MRI scans were acquired over 4 years.
- Participants were classified using the A/T/(N) framework.
Main Results:
- Elevated baseline sTREM2 levels correlated with accelerated cortical thinning in the temporal lobe and hippocampal atrophy.
- This association was independent of age, Aβ42, and total tau levels.
- The effect of sTREM2 on atrophy was more pronounced in individuals with high phosphorylated tau (p-tau) levels, suggesting a link with tau pathology.
Conclusions:
- Increased CSF sTREM2 is associated with accelerated brain atrophy in cognitively unimpaired older adults.
- Neuroinflammation, indicated by sTREM2, plays a role in neurodegeneration, particularly in the presence of tau pathology.
- Findings suggest a potential link between neuroinflammation, neurodegeneration, and amyloid-independent tauopathy.
