Sustained high body temperature exacerbates cognitive function and Alzheimer's disease-related pathologies

Area of Science:

• Neuroscience
• Public Health
• Environmental Health

Background:

• Global warming poses significant public health risks.
• Elevated body temperature is a risk factor for Alzheimer's disease (AD).
• The precise impact of high body temperature on cognitive function and AD pathology remains unclear.

Purpose of the Study:

• To investigate the effects of chronic high ambient temperature on cognitive function and AD pathologies in a mouse model.
• To elucidate the underlying molecular mechanisms linking elevated body temperature to AD pathogenesis.

Main Methods:

• Tg2576 mice were housed at either 23°C (control) or 30°C (high temperature) for 13 months.
• Evaluated cognitive function (memory impairment).
• Assessed key AD pathological markers, including amyloid-beta (Aβ) peptides, BACE1, neprilysin (NEP), heat shock proteins (HSPs), stress-stimulated kinases (JNK), total tau, and tau phosphorylation.

Main Results:

• Mice at 30°C exhibited increased body temperature, memory impairment, and enhanced Aβ generation.
• Elevated Aβ generation was linked to increased BACE1 and decreased NEP levels.
• High body temperature also increased HSPs, JNK, total tau, and tau phosphorylation.

Conclusions:

• Sustained high body temperature exacerbates cognitive decline and AD pathologies.
• The study provides mechanistic insights into how elevated body temperature contributes to AD.
• Findings suggest high body temperature as a modifiable factor for AD prevention.