# Genetic and Molecular Insights into the Links Between Heat Stroke, Alzheimer’s Disease, and Down Syndrome: A Mini-Review

## TL;DR

Heat stroke may worsen dementia disorders like Alzheimer’s and Down syndrome by increasing amyloid-β protein, which is linked to cognitive decline.

## Contribution

This paper connects heat stroke to Alzheimer’s and Down syndrome through shared molecular mechanisms involving amyloid-β.

## Key findings

- Heat stroke increases amyloid-β precursor protein gene expression and activates amyloid processing pathways.
- Down syndrome shares similar amyloid-β overexpression features with Alzheimer’s disease.
- Heat stroke could accelerate intellectual decline in individuals with Down syndrome.

## Abstract

Both epidemiological and animal model studies have revealed that heat stroke is closely related to the development or exacerbation of dementia disorders. The most common form of dementia is Alzheimer’s disease, which is characterized by the accumulation of amyloid-β protein in the central nervous system. Notably, a whole-genome transcriptome analysis of heat stroke patients has identified the increased expression of amyloid-β precursor protein gene and the activation of amyloid processing pathways. This finding provides a molecular basis for the theory that heat stroke is a risk factor for dementia disorders. Down syndrome—a common chromosomal abnormality—is also a dementia disorder that is characterized by the overexpression of amyloid-β precursor protein gene and the accumulation of amyloid-β protein. Thus, heat stroke may also develop or exacerbate Alzheimer’s disease-like dementia in Down syndrome. For individuals with Down syndrome, heat stroke is therefore not only a life-threatening risk factor but may also be a risk factor for accelerating intellectual decline.