Amyloid beta denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid-beta precursor protein (APP), which is cleaved by beta secretase and gamma secretase to yield Aβ in a cholesterol-dependent process and substrate presentation. Both neurons and oligodendrocytes produce and release Aβ in the brain, contributing to formation of amyloid plaques. Aβ molecules can aggregate to form flexible soluble oligomers which may exist in several forms. It is now believed that certain misfolded oligomers can induce other Aβ molecules to also take the misfolded oligomeric form, leading to a chain reaction akin to a prion infection. The oligomers are toxic to nerve cells. The other protein implicated in Alzheimer's disease, tau protein, also forms such prion-like misfolded oligomers, and there is some evidence that misfolded Aβ can induce tau to misfold.
Amyloid-beta precursor protein (APP) is an integral membrane protein expressed in many tissues and concentrated in the synapses of neurons. It functions as a cell surface receptor and has been implicated as a regulator of synapse formation, neural plasticity, antimicrobial activity, and iron export. It is coded for by the gene APP and regulated by substrate presentation. APP is best known as the precursor molecule whose proteolysis generates amyloid beta (Aβ), a polypeptide containing 37 to 49 amino acid residues, whose amyloid fibrillar form is the primary component of amyloid plaques found in the brains of Alzheimer's disease patients.
Amyloid plaques are extracellular deposits of amyloid beta (Aβ) protein that present mainly in the grey matter of the brain. Degenerative neuronal elements and an abundance of microglia and astrocytes can be associated with amyloid plaques. Some plaques occur in the brain as a result of aging, but large numbers of plaques and neurofibrillary tangles are characteristic features of Alzheimer's disease. The plaques are highly variable in shape and size; in tissue sections immunostained for Aβ, they comprise a log-normal size distribution curve, with an average plaque area of 400-450 square micrometers (μm2). The smallest plaques, which often consist of diffuse deposits of Aβ, are particularly numerous. Plaques form when Aβ misfolds and aggregates into oligomers and longer polymers, the latter of which are characteristic of amyloid.
Cerebral amyloid angiopathy (CAA) is a form of angiopathy in which amyloid beta peptide deposits in the walls of small to medium blood vessels of the central nervous system and meninges. The term congophilic is sometimes used because the presence of the abnormal aggregations of amyloid can be demonstrated by microscopic examination of brain tissue after staining with Congo red. The amyloid material is only found in the brain and as such the disease is not related to other forms of amyloidosis.
A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their death. Neurodegenerative diseases include amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, multiple system atrophy, tauopathies, and prion diseases. Neurodegeneration can be found in the brain at many different levels of neuronal circuitry, ranging from molecular to systemic.Because there is no known way to reverse the progressive degeneration of neurons, these diseases are considered to be incurable; however research has shown that the two major contributing factors to neurodegeneration are oxidative stress and inflammation. Biomedical research has revealed many similarities between these diseases at the subcellular level, including atypical protein assemblies and induced cell death. These similarities suggest that therapeutic advances against one neurodegenerative disease might ameliorate other diseases as well.
Beta-secretase 1, also known as beta-site amyloid precursor protein cleaving enzyme 1, beta-site APP cleaving enzyme 1 (BACE1), membrane-associated aspartic protease 2, memapsin-2, aspartyl protease 2, and ASP2, is an enzyme that in humans is encoded by the BACE1 gene. Expression of BACE1 is observed mainly in neurons and oligodendrocytes.
Early-onset Alzheimer's disease (EOAD), also called younger-onset Alzheimer's disease (YOAD), is Alzheimer's disease diagnosed before the age of 65. It is an uncommon form of Alzheimer's, accounting for only 5–10% of all Alzheimer's cases. About 60% have a positive family history of Alzheimer's and 13% of them are inherited in an autosomal dominant manner. Most cases of early-onset Alzheimer's share the same traits as the "late-onset" form and are not caused by known genetic mutations. Little is understood about how it starts.
Solanezumab is a monoclonal antibody being investigated by Eli Lilly as a neuroprotector for patients with Alzheimer's disease. The drug originally attracted extensive media coverage proclaiming it a breakthrough, but it has failed to show promise in Phase III trials.
PBT2 is a safe-for-human-use Zinc ionophore and an experimental drug candidate. It is a second-generation 8-hydroxyquinoline analog intended to be a successor to clioquinol and a potential treatment of Alzheimer's disease and Huntington's disease.
The biomarkers of Alzheimer's disease are neurochemical indicators used to assess the risk or presence of the disease. The biomarkers can be used to diagnose Alzheimer's disease (AD) in a very early stage, but they also provide objective and reliable measures of disease progress. It is imperative to diagnose AD disease as soon as possible, because neuropathologic changes of AD precede the symptoms by years. It is well known that amyloid beta (Aβ) is a good indicator of AD disease, which has facilitated doctors to accurately pre-diagnose cases of AD. When Aβ peptide is released by proteolytic cleavage of amyloid-beta precursor protein, some Aβ peptides that are solubilized are detected in CSF and blood plasma which makes AB peptides a promising candidate for biological markers. It has been shown that the amyloid beta biomarker shows 80% or above sensitivity and specificity, in distinguishing AD from dementia. It is believed that amyloid beta as a biomarker will provide a future for diagnosis of AD and eventually treatment of AD.
Rivastigmine, sold under the brand name Exelon among others, is an acetylcholinesterase inhibitor used for the treatment of dementia associated with Alzheimer's disease and with Parkinson's disease. Rivastigmine can be administered orally or via a transdermal patch; the latter form reduces the prevalence of side effects, which typically include nausea and vomiting.
Rudolph Emile 'Rudy' Tanzi a professor of Neurology at Harvard University, vice-chair of neurology, director of the Genetics and Aging Research Unit, and co-director of the Henry and Allison McCance Center for Brain Health at Massachusetts General Hospital (MGH).
p3 peptide also known as amyloid β- peptide (Aβ)17–40/42 is the peptide resulting from the α- and γ-secretase cleavage from the amyloid precursor protein (APP). It is known to be the major constituent of diffuse plaques observed in Alzheimer's disease (AD) brains and pre-amyloid plaques in people affected by Down syndrome. However, p3 peptide's role in these diseases is not truly known yet.
Florbetaben, sold under the brand name Neuraceq, is a diagnostic radiotracer developed for routine clinical application to visualize β-amyloid plaques in the brain. It is a fluorine-18 (18F)-labeled stilbene derivative.
The ion channel hypothesis of Alzheimer's disease (AD), also known as the channel hypothesis or the amyloid beta ion channel hypothesis, is a more recent variant of the amyloid hypothesis of AD, which identifies amyloid beta (Aβ) as the underlying cause of neurotoxicity seen in AD. While the traditional formulation of the amyloid hypothesis pinpoints insoluble, fibrillar aggregates of Aβ as the basis of disruption of calcium ion homeostasis and subsequent apoptosis in AD, the ion channel hypothesis in 1993 introduced the possibility of an ion-channel-forming oligomer of soluble, non-fibrillar Aβ as the cytotoxic species allowing unregulated calcium influx into neurons in AD.
Lecanemab, sold under the brand name Leqembi, is a monoclonal antibody medication used for the treatment of Alzheimer's disease. Lecanemab is an amyloid beta-directed antibody. It is given via intravenous infusion to patients with mild cognitive impairment or mild dementia. In clinical trials, it demonstrated modest efficacy in reducing relative cognitive decline compared to placebo. The most common side effects of lecanemab include headache, infusion-related reactions, and amyloid-related imaging abnormalities, a side effect known to occur with the class of antibodies targeting amyloid.
Phenserine is a synthetic drug which has been investigated as a medication to treat Alzheimer's disease (AD), as the drug exhibits neuroprotective and neurotrophic effects.
Donanemab, sold under the brand name Kisunla, is a monoclonal antibody used for the treatment of Alzheimer's disease. Donanemab was developed by Eli Lilly and Company.
Alzheimer's disease (AD) in the Hispanic/Latino population is becoming a topic of interest in AD research as Hispanics and Latinos are disproportionately affected by Alzheimer's Disease and underrepresented in clinical research. AD is a neurodegenerative disease, characterized by the presence of amyloid-beta plaques and neurofibrillary tangles, that causes memory loss and cognitive decline in its patients. However, pathology and symptoms have been shown to manifest differently in Hispanic/Latinos, as different neuroinflammatory markers are expressed and cognitive decline is more pronounced. Additionally, there is a large genetic component of AD, with mutations in the amyloid precursor protein (APP), Apolipoprotein E APOE), presenilin 1 (PSEN1), bridging Integrator 1 (BIN1), SORL1, and Clusterin (CLU) genes increasing one's risk to develop the condition. However, research has shown these high-risk genes have a different effect on Hispanics and Latinos then they do in other racial and ethnic groups. Additionally, this population experiences higher rates of comorbidities, that increase their risk of developing AD. Hispanics and Latinos also face socioeconomic and cultural factors, such as low income and a language barrier, that affect their ability to engage in clinical trials and receive proper care.
Alzheimer's disease (AD) in African Americans is becoming a rising topic of interest in AD care, support, and scientific research, as African Americans are disproportionately affected by AD. Recent research on AD has shown that there are clear disparities in the disease among racial groups, with higher prevalence and incidence in African Americans than the overall average. Pathologies for Alzheimer’s also seem to manifest differently in African Americans, including with neuroinflammation markers, cognitive decline, and biomarkers. Although there are genetic risk factors for Alzheimer’s, these account for few cases in all racial groups.
