Neurodegeneration as Convergent Three-Pathway Failure: A Unified Framework for Alzheimer’s and Related Dementias

Alzheimer’s and related dementias are not inevitable consequences of aging. This manuscript proposes that they arise when cumulative stress exceeds the repair capacity of three biological systems critical for maintaining brain health: proteostatic capacity, mitochondrial function, and neuroimmune regulation. In most cases, key influences such as genetics, environmental exposures, and health history are not primary determinants; they modify the baseline load borne by these pathways, influencing not only whether it is approaching a threshold, but how quickly it reaches the tipping point. To illustrate how diverse influences accumulate, the analysis maps 18 modifiable dementia risk factors onto the three convergent pathways. This approach reframes neurodegenerative risk as a dynamic, cumulative process and highlights opportunities for individualized assessment and targeted mitigation strategies long before dementia symptoms emerge.