Although plaques are one of the hallmarks of the disease, they're probably not the cause. As you pointed out, healthy brain tissue contains plaques, and plaque formation isn't necessarily correlated with the progression of the disease.
However, beta-amyloid seems to play a significant role. "Older" patients with Down's syndrome often develop Alzheimer's disease, and this is thought to be due to additional expression of APP (amyloid precursor protein), which is the precursor of beta-amyloid. The gene for APP is found on chromosome 21, the extra chromosome found in Down's syndrome patients. People with early-onset forms of Alzheimer's often have mutations in genes that are related to APP processing. Beta-amyloid seems to be upstream in the pathway that causes the hyperphosphorylation of tau, which is the protein involved in tangles, the other hallmark of the disease. Vaccination experiments involving beta-amyloid show reduced neurotoxicity and the resoration of long-term potentiation (LTP), a mechanism involved in memory formation.
In spite of all this evidence, APP and beta-amyloid are found in healthy brain tissue, so there's something else at work that involves beta-amyloid but not plaques. Some researchers believe that small, soluble oligomers of beta-amyloid (sometimes referred to as ADDLs) are the neurotoxic forms of amyloid-beta. ADDLs retard LTP, and they specifically target synapses. LTP is restored by vaccinations against ADDLs.
So what causes ADDL formation? Unfortunately, we don't know. Beta-amyloid may turn out to be a "cause" of Alzheimer's disease, but in turn, there must be a reason why the body loses the ability to keep beta-amyloid in check.
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Although plaques are one of the hallmarks of the disease, they're probably not the cause. As you pointed out, healthy brain tissue contains plaques, and plaque formation isn't necessarily correlated with the progression of the disease.
However, beta-amyloid seems to play a significant role. "Older" patients with Down's syndrome often develop Alzheimer's disease, and this is thought to be due to additional expression of APP (amyloid precursor protein), which is the precursor of beta-amyloid. The gene for APP is found on chromosome 21, the extra chromosome found in Down's syndrome patients. People with early-onset forms of Alzheimer's often have mutations in genes that are related to APP processing. Beta-amyloid seems to be upstream in the pathway that causes the hyperphosphorylation of tau, which is the protein involved in tangles, the other hallmark of the disease. Vaccination experiments involving beta-amyloid show reduced neurotoxicity and the resoration of long-term potentiation (LTP), a mechanism involved in memory formation.
In spite of all this evidence, APP and beta-amyloid are found in healthy brain tissue, so there's something else at work that involves beta-amyloid but not plaques. Some researchers believe that small, soluble oligomers of beta-amyloid (sometimes referred to as ADDLs) are the neurotoxic forms of amyloid-beta. ADDLs retard LTP, and they specifically target synapses. LTP is restored by vaccinations against ADDLs.
So what causes ADDL formation? Unfortunately, we don't know. Beta-amyloid may turn out to be a "cause" of Alzheimer's disease, but in turn, there must be a reason why the body loses the ability to keep beta-amyloid in check.