A comprehensive multiomics approach toward understanding the relationship between aging and dementia

Area of Science:

• Neuroscience
• Gerontology
• Pharmacology

Background:

• Age is the primary risk factor for sporadic Alzheimer's disease (AD).
• Aging processes may directly contribute to AD pathogenesis.
• The neurotrophic drug J147 was developed using screens for age-associated neurotoxicity.

Purpose of the Study:

• To test the efficacy of J147 against AD pathology in rapidly aging SAMP8 mice.
• To identify molecular mechanisms linking aging to AD using an integrative multiomics approach.

Main Methods:

• Phenotypic screening for neurotrophic drug development.
• Administration of J147 to old and young SAMP8 mice.
• Multiomics analysis including proteomics, transcriptomics, metabolomics, and cognitive testing.

Main Results:

• J147 significantly reduced cognitive deficits in old SAMP8 mice.
• J147 treatment normalized molecular markers related to AD pathology, vascular issues, synaptic function, and inflammation.
• Molecular profiles of treated old mice approached those of young mice.

Conclusions:

• J147 demonstrates therapeutic potential for age-related cognitive decline and AD.
• The study identified key molecular changes associated with aging that are critical for AD development.
• J147's ability to reverse multiple aging-related pathologies highlights its broad neuroprotective effects.