A new study published in Nature Neuroscience has revealed groundbreaking findings on the role of TREM1 in disrupting myeloid bioenergetics and cognitive function in aging and Alzheimer’s disease mouse models. The research, conducted by a team of scientists led by Edward N. Wilson, sheds light on the potential implications for neurodegenerative diseases.

The study highlights the impact of Trem1 deficiency in preventing age-dependent changes in myeloid metabolism, inflammation, and hippocampal memory function in mice. The findings suggest that Trem1 deficiency rescues age-associated declines in ribose 5-phosphate and protects against amyloid-β42 oligomer-induced bioenergetic changes in microglia.

Furthermore, the research demonstrates that Trem1 haploinsufficiency in the 5XFAD mouse model prevents spatial memory loss, preserves homeostatic microglial morphology, and reduces neuritic dystrophy. In aging APPSwe mice, Trem1 deficiency prevents hippocampal memory decline while restoring synaptic mitochondrial function and cerebral glucose uptake.

The study also provides insights from postmortem Alzheimer’s disease brain samples, revealing the colocalization of TREM1 with Iba1+ cells around amyloid plaques. The expression of TREM1 is associated with Alzheimer’s disease clinical and neuropathological severity, indicating its potential role in promoting cognitive decline in aging and in the context of amyloid pathology.

These findings have significant implications for understanding the mechanisms underlying neurodegenerative diseases, particularly Alzheimer’s disease. The research opens new avenues for exploring the role of TREM1 and myeloid metabolism in the development and progression of cognitive impairments associated with aging and neurodegenerative conditions.