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MOLECULAR CHARACTERIZATION OF SELECTIVELY VULNERABLE NEURONS IN ALZHEIMER’S DISEASE
It is known that, in the case of neurodegenerative diseases such as Parkinson’s disease and amyotrophic lateral sclerosis (ALS), the neurons are the first cells to die, but this is not the case with Alzheimer’s disease, since the neurons and brain regions are not the same. In the course of the disease, certain parts of the brain, such as the caudal entorhinal cortex, are affected early on, while others, such as the superior frontal gyrus, suffer atrophy later on. A group of molecular researchers and neuropathologists from the Weill Institute for Neurosciences at the University of California, San Francisco, has undertaken a study to characterize the impact of the progression of the disease on different types of cellular subpopulations, which can be defined independently of the effect of the advance of Alzheimer’s disease.
It is important to underline that a vulnerable subpopulation of the excitatory neurons was identified in the entorhinal cortex and their selective depletion during the progress of the disease was validated by histopathological examination. Subpopulations of inhibitory neurons were also examined, but did not show differences in terms of vulnerability. Finally, an astrocyte subpopulation was discovered, likely representing reactive astrocytes, characterized by decreased expression of genes involved in homeostatic functions.
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According to the researchers, this new characterization of the vulnerable neurons in Alzheimer’s disease paves the way for future mechanistic studies of selective vulnerability and potential therapeutic strategies for enhancing neuronal resilience.
Source: Kun Leng et al., “Molecular characterization of selectively vulnerable neurons in Alzheimer’s disease.” Nature Neuroscience 24 (11 January 2021).
