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| title | chunk | source | category | tags | date_saved | instance |
|---|---|---|---|---|---|---|
| Alzheimer's disease | 4/12 | https://en.wikipedia.org/wiki/Alzheimer's_disease | reference | science, encyclopedia | 2026-05-05T11:04:11.975566+00:00 | kb-cron |
==== Infection ==== The possibility that infectious agents cause Alzheimer's disease has been considered since the early 20th century, when Oskar Fischer likened amyloid plaques to small masses (called 'Drusen') of a microbe called actinomyces. Since then, at least 15 different agents, including bacteria, viruses, fungi and protozoa, have been proposed to cause Alzheimer's disease. No definitive evidence has been presented that a specific infectious agent is necessary and sufficient to cause Alzheimer's disease. However, it is possible that microbial infections might act as risk factors for the disease. For example, human herpes viruses such as HSV-1, HHV-6, and HHV-7 have been linked to the risk of Alzheimer's disease. In addition, some pathogens have been reported to seed Aβ deposition in the brain, and aggregated Aβ has antimicrobial properties, suggesting that Aβ plaques might form when brain cells generate Aβ to fight infection. Researchers caution that brain infections can cause dementia by mechanisms unrelated to Alzheimer's disease.
==== DNA damage ==== DNA damage accumulates in affected brains; reactive oxygen species may be the major source of this DNA damage.
==== Cholinergic ==== The cholinergic hypothesis proposes that the loss of neurons in the basal forebrain, which produce the neurotransmitter acetylcholine, is a key event in the pathogenesis of Alzheimer's disease. These cells supply acetylcholine to synapses in the limbic system and cerebral cortex. The cholinergic hypothesis led to the development of drugs that increase acetylcholine in the brains of Alzheimer patients. The efficacy of these agents is limited, probably because many other neurotransmitter systems degenerate in Alzheimer's disease.
==== Sleep ==== Sleep disturbances are seen as a possible risk factor for inflammation in Alzheimer's disease. Sleep disruption was previously only seen as a consequence of Alzheimer's disease, but as of 2020, accumulating evidence suggests that this relationship may be bidirectional.
==== Neuroinflammation, metal toxicity, smoking, and air pollution ==== Systemic markers of the innate immune system are risk factors for late-onset Alzheimer's disease, and misfolded Aβ and tau proteins both are associated with oxidative stress and neuroinflammation. Chronic inflammation also is a feature of other neurodegenerative diseases, including Parkinson's disease, and ALS. The cellular homeostasis of biometals such as ionic copper, iron, and zinc is disrupted in Alzheimer's disease, though it remains unclear whether this is produced by or causes the changes in proteins. Smoking is a significant Alzheimer's disease risk factor. Exposure to air pollution may be a contributing factor to the development of Alzheimer's disease.
==== Age-related myelin decline ==== Retrogenesis is a medical hypothesis that just as the fetus goes through a process of neurodevelopment beginning with neurulation and ending with myelination, the brains of people with Alzheimer's disease go through a reverse neurodegeneration process starting with demyelination and death of axons (white matter) and ending with the death of grey matter. Likewise the hypothesis is, that as infants go through states of cognitive development, people with Alzheimer's disease go through the reverse process of progressive cognitive impairment. According to one theory, dysfunction of oligodendrocytes and their associated myelin during aging contributes to axon damage, which in turn generates amyloid production and tau hyperphosphorylation. Comorbidities between the demyelinating disease, multiple sclerosis, and Alzheimer's disease have been reported.
==== Other hypotheses ====
The association with celiac disease is unclear, with a 2019 study finding no increase in dementia overall in those with celiac disease, while a 2018 review found an association with several types of dementia, including Alzheimer's disease. Studies have reported a potential link between infection with certain viruses and developing Alzheimer's disease later in life. Notably, a large scale study conducted on 6,245,282 patients has reported an increased risk of developing Alzheimer's disease following COVID-19 infection in cognitively normal individuals over 65. Some evidence suggests that some viral infections, such as Herpes simplex virus 1 (HSV-1), may be associated with dementia. However, studies have shown conflicting results, and the association with Alzheimer's is unclear as of 2024. Some researchers have proposed that Alzheimer's disease is Type 3 diabetes because of a number of correspondences with both Type 1 and Type 2 diabetes.
== Pathophysiology ==
=== Neuropathology ===