APOE occurs in three common forms alleles: But APOE is also independently synthesized in brain astrocytes and, to a lesser extent in brain oligodendrocytes — and does not cross the blood-brain barrier. Cholesterol is an essential constituent of all cell membranes, which helps provide membrane fluidity. The human brain has high levels of myelin to facilitate axon conduction speed and information processing.
Repeats same conversations More abusive, anxious, or paranoid The disease course is divided into four stages, with a progressive pattern of cognitive and functional impairment.
Pre-dementia The first symptoms are often mistakenly attributed to ageing or stress.
In a small percentage, difficulties with language, executive functions, perception agnosiaor execution of movements apraxia are more prominent than memory problems.
Reading and writing skills are also progressively lost. Common manifestations are wanderingirritability and labile affectleading to crying, outbursts of unpremeditated aggressionor resistance to caregiving.
Although aggressiveness can still be present, extreme apathy and exhaustion are much more common symptoms. The cause of death is usually an external factor, such as infection of pressure ulcers or pneumonianot the disease itself.
Most of autosomal dominant familial AD can be attributed to mutations in one of three genes: Cholinergic hypothesis The oldest, on which most currently available drug therapies are based, is the cholinergic hypothesis,  which proposes that AD is caused by reduced synthesis of the neurotransmitter acetylcholine.
The cholinergic hypothesis has not maintained widespread support, largely because medications intended to treat acetylcholine deficiency have not been very effective.
While apolipoproteins enhance the breakdown of beta amyloid, some isoforms are not very effective at this task such as APOE4leading to excess amyloid buildup in the brain.
These toxic oligomers, also referred to as amyloid-derived diffusible ligands ADDLsbind to a surface receptor on neurons and change the structure of the synapse, thereby disrupting neuronal communication. In this model, beta-amyloid plays a complementary role, by depressing synaptic function.
In earlya trial of verubecestatwhich inhibits the beta-secretase protein responsible for creating beta-amyloid protein was discontinued as an independent panel found "virtually no chance of finding a positive clinical effect". The tau hypothesis proposes that tau protein abnormalities initiate the disease cascade.
Eventually, they form neurofibrillary tangles inside nerve cell bodies. These ions affect and are affected by tau, APP, and APOE,  and their dysregulation may cause oxidative stress that may contribute to the pathology.
This loss results in gross atrophy of the affected regions, including degeneration in the temporal lobe and parietal lobeand parts of the frontal cortex and cingulate gyrus.
Tangles neurofibrillary tangles are aggregates of the microtubule-associated protein tau which has become hyperphosphorylated and accumulate inside the cells themselves. Although many older individuals develop some plaques and tangles as a consequence of ageing, the brains of people with AD have a greater number of them in specific brain regions such as the temporal lobe.
The beta-amyloid fragment is crucial in the formation of senile plaques in AD. APP is critical to neuron growth, survival, and post-injury repair. Every neuron has a cytoskeletonan internal support structure partly made up of structures called microtubules.
These microtubules act like tracks, guiding nutrients and molecules from the body of the cell to the ends of the axon and back. A protein called tau stabilises the microtubules when phosphorylatedand is therefore called a microtubule-associated protein.
Inflammation is a general marker of tissue damage in any disease, and may be either secondary to tissue damage in AD or a marker of an immunological response. Obesity and systemic inflammation may interfere with immunological processes which promote disease progression.Alzheimers disease: Neurobiology, causes and treatments of Alzheimer's Disease (AD) is one of the most common of the dementing illnesses.
A progressive, degenerative disease that attacks the brain, causing impaired memory, thinking and behavior. Variations of the β-amyloid theory of Alzheimer's disease (AD) have commanded a remarkable degree of academic consensus in the field for the last 20 years.
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Professional membership is for scientists, physicians and other professionals involved in the causes and treatments of Alzheimer's disease and related disorders. Alzheimer's disease (AD) is devastating neurodegenerative disease, the most common among the dementing illnesses. The neuropathological hallmarks of AD include extracellular β-amyloid (amyloid precursor protein (APP) deposits, intracellular neurofibrillary tangles (NFT)), dystrophic neuritis, and amyloid angiopathy.