Spirochete infections have also been linked to dementia. DNA damages accumulate in AD brains; reactive oxygen species may be the major source of this DNA damage.Sleep disturbances are seen as a possible risk factor for inflammation in Alzheimers disease. Sleep problems have been seen as a consequence of Alzheimers disease but studies suggest that they may instead be a causal factor. Sleep disturbances are thought to be linked to persistent inflammation. The cellular homeostasis of biometals such as ionic copper, iron, and zinc is disrupted in Alzheimers disease, though it remains unclear whether this is produced by or causes the changes in proteins. Smoking is a significant Alzheimers disease risk factor. Systemic markers of the innate immune system are risk factors for late-onset Alzheimers disease. Exposure to air pollution may be a contributing factor to the development of Alzheimers disease.One hypothesis posits that dysfunction of oligodendrocytes and their associated myelin during aging contributes to axon damage, which then causes amyloid production and tau hyper-phosphorylation as a side effect. 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 Alzheimers 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 Alzheimers disease go through the reverse process of progressive cognitive impairment.The association with celiac disease is unclear, with a 2019 study finding no increase in dementia overall in those with CD, while a 2018 review found an association with several types of dementia including Alzheimers disease. Pathophysiology
Neuropathology
Alzheimers disease is characterised by loss of neurons and synapses in the cerebral cortex and certain subcortical regions. This loss results in gross atrophy of the affected regions, including degeneration in the temporal lobe and parietal lobe, and parts of the frontal cortex and cingulate gyrus. Degeneration is also present in brainstem nuclei particularly the locus coeruleus in the pons. Studies using MRI and PET have documented reductions in the size of specific brain regions in people with Alzheimers disease as they progressed from mild cognitive impairment to Alzheimers disease, and in comparison with similar images from healthy older adults.Both Aβ plaques and neurofibrillary tangles are clearly visible by microscopy in brains of those with Alzheimers disease, especially in the hippocampus. However, Alzheimers disease may occur without neurofibrillary tangles in the neocortex. Plaques are dense, mostly insoluble deposits of beta-amyloid peptide and cellular material outside and around neurons. Tangles (neurofibrillary tangles) are aggregates of the microtubule-associated protein tau which has become hyperphosphorylated and accumulate inside the cells themselves.