Dystrophic microglia are associated with neurodegenerative disease and not healthy aging in the human brain.

Loss of physiological microglial function may increase the propagation of neurodegenerative diseases. Cellular senescence is a hallmark of aging; thus, we hypothesized age could be a cause of dystrophic microglia. Stereological counts were performed for total microglia, 2 microglia morphologies (hypertrophic and dystrophic) across the human lifespan. An age-associated increase in the number of dystrophic microglia was found in the hippocampus and frontal cortex. However, the increase in dystrophic microglia was proportional to the age-related increase in the total number of microglia. Thus, aging alone does not explain the presence of dystrophic microglia. We next tested if dystrophic microglia could be a disease-associated microglia morphology. Compared with controls, the number of dystrophic microglia was greater in cases with either Alzheimer's disease, dementia with Lewy bodies, or limbic-predominant age-related TDP-43 encephalopathy. These results demonstrate that microglia dystrophy, and not hypertrophic microglia, are the disease-associated microglia morphology. Finally, we found strong evidence for iron homeostasis changes in dystrophic microglia, providing a possible molecular mechanism driving the degeneration of microglia in neurodegenerative disease.

Long-standing multiple sclerosis neurodegeneration: volumetric magnetic resonance imaging comparison to Parkinson's disease, mild cognitive impairment, Alzheimer's disease, and elderly healthy controls.

Multiple sclerosis (MS) exhibits neurodegeneration driven disability progression. We compared the extent of neurodegeneration among 112 long-standing MS patients, 37 Parkinson's disease (PD) patients, 34 amnestic mild cognitive impairment (aMCI) patients, 37 Alzheimer's disease (AD) patients, and 184 healthy controls. 3T MRI volumes of whole brain (WBV), white matter (WMV), gray matter (GMV), cortical (CV), deep gray matter (DGM), and nuclei-specific volumes of thalamus, caudate, putamen, globus pallidus, and hippocampus were derived with SIENAX and FIRST software. Аge and sex-adjusted analysis of covariance was used. WBV was not significantly different between diseases. MS had significantly lower WMV compared to other disease groups (p < 0.021). Only AD had smaller GMV and CV when compared to MS (both p < 0.001). MS had smaller DGM volume than PD and aMCI (p < 0.001 and p = 0.026, respectively) and lower thalamic volume when compared to all other neurodegenerative diseases (p < 0.008). Long-standing MS exhibits comparable global atrophy with lower WMV and thalamic volume when compared to other classical neurodegenerative diseases.