The causes of Alzheimer’s disease

“Alzheimer’s disease is a progressive neurologic disorder that causes the brain to shrink (atrophy) and brain cells to die. Alzheimer’s disease is the most common cause of dementia — a continuous decline in thinking, behavioral and social skills that affects a person’s ability to function independently” (from the Mayo Clinic).

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*Tang, Y., Zhang, D., Gong, X., & Zheng, J. (2022). A mechanistic survey of Alzheimer’s disease. Biophysical Chemistry, 281, 106735.

Alzheimer’s disease (AD) is the most common, age-dependent neurodegenerative disorder, affecting ~50 million people worldwide. While AD has been intensively studied from different aspects, there is no effective cure for AD, largely due to a lack of a clear mechanistic understanding of AD. AD is associated with progressive neuronal loss and synaptic dysfunction, accompanied by the presence of senile plaques of amyloid-β (Aβ) and the intracellular neurofibrillary tangles of tau in the elderly brains. In this mini-review, we mainly focus on the discussion and summary of mechanistic causes of Alzheimer’s disease (AD).

As a multifactorial and chronic disease, different risk factors, including genetic factors, age, environmental factors, head injuries, infections, and vascular diseases have been reported to contribute to the cause of neurodegeneration in the brain of AD patients. While different AD mechanisms illustrate different molecular and cellular pathways in AD pathogenesis, they do not necessarily exclude each other. Instead, some of them could work together to initiate, trigger, and promote the onset and development of AD.

In a broader viewpoint, some AD mechanisms (e.g., amyloid aggregation mechanism, microbial infection/neuroinflammation mechanism, and amyloid cross-seeding mechanism) could also be applicable to other amyloid diseases including type II diabetes, Parkinson’s disease, and prion disease. Such common mechanisms for AD and other amyloid diseases explain not only the pathogenesis of individual amyloid diseases, but also the spreading of pathologies between these diseases, which will inspire new strategies for therapeutic intervention and prevention for AD.”

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