Genetic overlap between Alzheimer’s disease, amyotrophic lateral sclerosis, Lewy body dementia, and Parkinson’s disease

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Biomedical research has revealed many similarities between neurodegenerative diseases at the cellular level, including atypical protein assemblies. These similarities suggest that therapeutic advances against one neurodegenerative disease might ameliorate other diseases as well. enter image description here In each disease, neurons gradually lose function as the disease progresses with age. It is though that repeated viral exposures, even seemingly innocuous, can significantly elevate risks of neurodegenerative disease, including up to 15 years after infection.

Yet the search for a specific viral or auto-immune origin in these diseases have mostly failed. This article published on medRxiv by scientists from Netherlands, aims at identifying overlap at genetic level between four investigated neurodegenerative disorders (Alzheimer’s disease, amyotrophic lateral sclerosis, Lewy body dementia, and Parkinson’s disease).

As these diseases are mostly associated with age, they have a poor heritability, so it would be difficult to associate with some gene.

As in previous studies, the authors failed to identify any region, gene, gene-set, cell or tissue type that was shared between all four neurodegenerative diseases. However, they found that HLA locus was significantly associated with these traits. It is not clear how it is associated because the scientists used a tool named FUMA. FUMA is an automatic tool which annotates GWAS findings and prioritizes the most likely causal SNPs and genes. Yet it is a bit obscure like all these "ontological" tools, like too often in molecular biology it is a qualitative, not quantitative tool.

HLA is a part of the genome which plays an important role in immune systems. The major histocompatibility complex (MHC) is a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell surface proteins essential for the adaptive immune system. This genetic complex is called HLA in humans.

These cell surface proteins are called MHC molecules. The proteins encoded by HLAs are those on the outer part of body cells that are (in effect) unique to that person. The immune system uses the HLAs to differentiate self cells and non-self cells. Any cell displaying that person's HLA type belongs to that person and is therefore not an invader.

While this study does not try to explain what is the relation between those diseases and the HLA region, it is possible to make some guesses.

If aging (and DNA) degradation is a function of the number of viral attacks during life, then it makes sense to find a correlation between immune system and these non-communicable diseases.

But again many studies have not found any relations between viral or auto-immune insults and neurodegenarative diseases.

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