Is sporadic Alzheimer's disease a developmental disorder?

Area of Science:

• Neuroscience
• Evolutionary Biology
• Pathology

Background:

• Alzheimer's disease (AD) is a human-specific neurodegenerative disorder with a long, silent preclinical phase.
• AD's clinical symptoms reflect a decline in functions acquired late in human evolution, mirroring developmental trajectories in reverse.
• Neurofibrillar degeneration, a hallmark of AD, disproportionately affects brain regions associated with encephalization and recent human evolution.

Purpose of the Study:

• To explore how phylogenetic and ontogenetic perspectives on brain development illuminate Alzheimer's disease.
• To investigate the relationship between cortical organization, evolutionary brain development, and AD pathology distribution.
• To consider molecular evidence suggesting a developmental origin for Alzheimer's disease.

Main Methods:

• Review of existing literature on Alzheimer's disease neuropathology.
• Analysis of neurofibrillar degeneration patterns in relation to brain evolution and development.
• Synthesis of findings from molecular biology studies on genomic mosaicism in AD.

Main Results:

• Neurofibrillar degeneration in AD follows a stereotypic sequence, inversely recapitulating human brain ontogeny and preferentially affecting evolutionarily recent cortical areas.
• The modular organization of the cerebral cortex, reflecting its development, influences the distribution of AD pathology.
• Evidence suggests a potential developmental origin for AD, supported by molecular studies.

Conclusions:

• Phylogenetic and ontogenetic dimensions of brain structure and function are crucial for understanding Alzheimer's disease.
• The unique vulnerability of human brain regions in AD is linked to evolutionary and developmental processes.
• Further research into the developmental origins of AD, including genomic factors, is warranted.