Alzheimer’s is a complex neurodegenerative disease that is a Protein Misfolding Disease (MFD) that is believed to account for 60% to 70% of dementia. Other MFDs include Parkinson’s, cataracts, cystic fibrosis, sickle cell disease, among others. It starts 20 to 30 years before many of the more severe neurodegenerative symptoms manifest.
About 1 to 5% of Alzheimer’s is early onset Alzheimer’s (EOAD). It is determined by a defect on chromosome 14. The more common remaining 95% is known as Sporadic Alzheimer’s and is not linked to genetics. There are many theories for the etiology of Alzheimer’s including prion infection, Aβ amyloid cascade hypothesis, Tau protein hyperphosphorylation, mitochondria cascade hypothesis, among others. While dementia was always associated with old age, it was not until 1907 that Alzheimer’s disease was identified.
Historically, a histopathological study led the German psychiatrist Alois Alzheimer to first report the disease. He found that the brain of his patient had distinctive plaques and tangles. The senile plaques are extra cellular deposits rich in Aβ protein aggregates, and the intracellular tangles are caused by a break down of the protein tau.
Aβ and Tau
The body produces a large protein containing 639 to 770 amino acids that is concentrated in the synapsis of neurons. It is called Amyloid Precursor Protein (APP). While the primary functioning of APP is not known, it is implicated in neural plasticity. In normal brains APP is proteolyzed (cut into smaller chains), and one smaller chain of 37 to 49 amino acids is beta amyloid (Aβ). A misfolding of APP is believed to produce a form of Aβ that is sticky. A single Aβ (monomer) sticks to another and another (oligomers) and eventually deposit as extracellular (outside neurons) senile plaque that are believed to be toxic to neurons. Senile plaque is a primary marker of Alzheimer’s.
Tau, a microtubule-associated protein (MAPT), is a protein that stabilizes microtubules within a neuron, analogous to bricks holding up a tunnel. Microtubules are channels used to transport molecules within a neuron. Tau break down and aggregate into neurofibrillary tangles (NFTs). Without the bricks holding tunnels together the microtubules fail and without an adequate microtubule infrastructure to transport molecules within a neuron, the neuron starves and dies. NFTs are also primary marker of Alzheimer’s.
There is preliminary evidence showing “the possibility that “seeds” of the Aβ protein involved in AD could be transmitted during procedures in which fluid or tissues from one person are introduced into another, such as blood transfusion, organ transplants and other common medical procedures.” (Alison Abbott, Nature March 17, 2016)