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Frontotemporal dementia (FTD), also called frontotemporal degeneration disease or frontotemporal neurocognitive disorder, encompasses several types of dementia involving the progressive degeneration of the brain's frontal and temporal lobes. Men and women appear to be equally affected. FTD generally presents as a behavioral or language disorder with gradual onset. Signs and symptoms tend to appear in late adulthood, typically between the ages of 45 and 65, although it can affect people younger or older than this. Currently, no cure or approved symptomatic treatment for FTD exists, although some off-label drugs and behavioral methods are prescribed.
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.
Frontotemporal lobar degeneration (FTLD) is a pathological process that occurs in frontotemporal dementia. It is characterized by atrophy in the frontal lobe and temporal lobe of the brain, with sparing of the parietal and occipital lobes.
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.
Neurofibrillary tangles (NFTs) are intracellular aggregates of hyperphosphorylated tau protein that are most commonly known as a primary biomarker of Alzheimer's disease. Their presence is also found in numerous other diseases known as tauopathies. Little is known about their exact relationship to the different pathologies.
Pittsburgh compound B (PiB) is a radioactive analog of thioflavin T, which can be used in positron emission tomography scans to image beta-amyloid plaques in neuronal tissue. Due to this property, Pittsburgh compound B may be used in investigational studies of Alzheimer's disease.
Tauopathies are a class of neurodegenerative diseases characterized by the aggregation of abnormal tau protein. Hyperphosphorylation of tau proteins causes them to dissociate from microtubules and form insoluble aggregates called neurofibrillary tangles. Various neuropathologic phenotypes have been described based on the anatomical regions and cell types involved as well as the unique tau isoforms making up these deposits. The designation 'primary tauopathy' is assigned to disorders where the predominant feature is the deposition of tau protein. Alternatively, diseases exhibiting tau pathologies attributed to different and varied underlying causes are termed 'secondary tauopathies'. Some neuropathologic phenotypes involving tau protein are Alzheimer's disease, frontotemporal dementia, progressive supranuclear palsy, and corticobasal degeneration.
Sir John Anthony Hardy is a human geneticist and molecular biologist at the Reta Lila Weston Institute of Neurological Studies at University College London with research interests in neurological diseases.
The Nun Study of Aging and Alzheimer's Disease is a continuing longitudinal study, begun in 1986, to examine the onset of Alzheimer's disease. David Snowdon, an Epidemiologist and the founding Nun Study investigator, started the Nun Study at the University of Minnesota, later transferring the study to the University of Kentucky in 1990. In 2008, with Snowdon's retirement, the study returned to the University of Minnesota. The Nun Study was very briefly moved from the University of Minnesota to Northwestern University in 2021 under the directorship of Dr. Margaret Flanagan. The Nun Study is currently housed at the University of Texas Health San Antonio in the Bigg's Institute for Alzheimer's and Neurodegenerative diseases under the continued directorship of Neuropathologist, Dr. Margaret Flanagan.
The prevention of dementia involves reducing the number of risk factors for the development of dementia, and is a global health priority needing a global response. Initiatives include the establishment of the International Research Network on Dementia Prevention (IRNDP) which aims to link researchers in this field globally, and the establishment of the Global Dementia Observatory a web-based data knowledge and exchange platform, which will collate and disseminate key dementia data from members states. Although there is no cure for dementia, it is well established that modifiable risk factors influence both the likelihood of developing dementia and the age at which it is developed. Dementia can be prevented by reducing the risk factors for vascular disease such as diabetes, high blood pressure, obesity, smoking, physical inactivity and depression. A study concluded that more than a third of dementia cases are theoretically preventable. Among older adults both an unfavorable lifestyle and high genetic risk are independently associated with higher dementia risk. A favorable lifestyle is associated with a lower dementia risk, regardless of genetic risk. In 2020, a study identified 12 modifiable lifestyle factors, and the early treatment of acquired hearing loss was estimated as the most significant of these factors, potentially preventing up to 9% of dementia cases.
Alzheimer's disease (AD) is a neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems with language, disorientation, mood swings, loss of motivation, self-neglect, and behavioral issues. As a person's condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the average life expectancy following diagnosis is three to twelve years.
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.
Samuel E. Gandy, is a neurologist, cell biologist, Alzheimer's disease (AD) researcher and expert in the metabolism of the sticky substance called amyloid that clogs the brain in patients with Alzheimer's. His team discovered the first drugs that could lower the formation of amyloid.
Alzheimer's Disease Neuroimaging Initiative (ADNI) is a multisite study that aims to improve clinical trials for the prevention and treatment of Alzheimer's disease (AD). This cooperative study combines expertise and funding from the private and public sector to study subjects with AD, as well as those who may develop AD and controls with no signs of cognitive impairment. Researchers at 63 sites in the US and Canada track the progression of AD in the human brain with neuroimaging, biochemical, and genetic biological markers. This knowledge helps to find better clinical trials for the prevention and treatment of AD. ADNI has made a global impact, firstly by developing a set of standardized protocols to allow the comparison of results from multiple centers, and secondly by its data-sharing policy which makes available all at the data without embargo to qualified researchers worldwide. To date, over 1000 scientific publications have used ADNI data. A number of other initiatives related to AD and other diseases have been designed and implemented using ADNI as a model. ADNI has been running since 2004 and is currently funded until 2021.
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.
Synucleinopathies are neurodegenerative diseases characterised by the abnormal accumulation of aggregates of alpha-synuclein protein in neurons, nerve fibres or glial cells. There are three main types of synucleinopathy: Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Other rare disorders, such as various neuroaxonal dystrophies, also have α-synuclein pathologies. Additionally, autopsy studies have shown that around 6% of sporadic Alzheimer's Disease exhibit α-synuclein positive Lewy pathology, and are sub-classed as Alzheimer's Disease with Amygdalar Restricted Lewy Bodies (AD/ALB).
Primary age-related tauopathy (PART) is a neuropathological designation introduced in 2014 to describe the neurofibrillary tangles (NFT) that are commonly observed in the brains of normally aged and cognitively impaired individuals that can occur independently of the amyloid plaques of Alzheimer's disease (AD). The term and diagnostic criteria for PART were developed by a large group of neuropathologists, spearheaded by Drs. John F. Crary and Peter T. Nelson. Despite some controversy, the term PART has been widely adopted, with the consensus criteria cited over 1130 times as of April 2023 according to Google Scholar.
LATE is a term that describes a prevalent medical condition with impaired memory and thinking in advanced age, often culminating in the dementia clinical syndrome. In other words, the symptoms of LATE are similar to those of Alzheimer's disease.
Julie C. Price is an American medical physicist and professor of radiology at Massachusetts General Hospital (MGH), Harvard Medical School (HMS), as well as the director of PET Pharmacokinetic Modeling at the Athinoula A. Martinos Center at MGH. Price is a leader in the study and application of quantitative positron emission tomography (PET) methods. Prior to this, Price worked with Pittsburgh colleagues to lead the first fully quantitative pharmacokinetic evaluations of 11C-labeled Pittsburgh compound-B (PIB), one of the most widely used PET ligands for imaging amyloid beta plaques. As a principal investigator at MGH, Price continues work to validate novel PET methods for imaging biological markers of health and disease in studies of aging and neurodegeneration, including studies of glucose metabolism, protein expression, neurotransmitter system function, and tau and amyloid beta plaque burden.
Howard H Feldman is a professor of neurosciences at the University of California, San Diego (UCSD). He was appointed director of the Alzheimer's Disease Cooperative Study (ADCS) in April 2016, a national grant-funded network and coordinating center that was established in 1991. He holds the Epstein Family Chancellor’s Chair in Alzheimer’s Disease Research at UC San Diego. Prior to joining UC San Diego, he was on faculty at University of British Columbia where he served as the Head of the Division of Neurology, the Director of the Alzheimer’s and Related Disorders Clinic and the Executive Associate Dean for Research for the Faculty of Medicine.
References
- 1 2 Patton, Charlie. "Mayo Clinic study finds men with Alzheimer's are misdiagnosed more often than women". The Florida Times-Union. Retrieved 2024-12-23.
- ↑ Murray, Melissa E. (2010). "Cerebral white matter hyperintensities : a synthesis of their clinico-radiologic and neuropathologic correlates in the non-demented elderly". WorldCat. Retrieved 2024-12-23.
- ↑ "Melissa E. Murray". orcid.org. Retrieved 2024-12-23.
- ↑ Ledger, Katie (2018-12-31). "Patients who make research happen". Port Charlotte Sun. pp. SEB1, . Retrieved 2024-12-22.
- ↑ Murray, Melissa E; Graff-Radford, Neill R; Ross, Owen A; Petersen, Ronald C; Duara, Ranjan; Dickson, Dennis W (September 2011). "Neuropathologically defined subtypes of Alzheimer's disease with distinct clinical characteristics: a retrospective study". The Lancet Neurology. 10 (9): 785–796. doi:10.1016/S1474-4422(11)70156-9. PMC 3175379 . PMID 21802369.
- ↑ Murray, Melissa E.; Lowe, Val J.; Graff-Radford, Neill R.; Liesinger, Amanda M.; Cannon, Ashley; Przybelski, Scott A.; Rawal, Bhupendra; Parisi, Joseph E.; Petersen, Ronald C.; Kantarci, Kejal; Ross, Owen A.; Duara, Ranjan; Knopman, David S.; Jack, Clifford R.; Dickson, Dennis W. (May 2015). "Clinicopathologic and 11 C-Pittsburgh compound B implications of Thal amyloid phase across the Alzheimer's disease spectrum". Brain. 138 (5): 1370–1381. doi:10.1093/brain/awv050. ISSN 0006-8950. PMC 4407190 . PMID 25805643.
- ↑ Crist, Angela M.; Hinkle, Kelly M.; Wang, Xue; Moloney, Christina M.; Matchett, Billie J.; Labuzan, Sydney A.; Frankenhauser, Isabelle; Azu, Nkem O.; Liesinger, Amanda M.; Lesser, Elizabeth R.; Serie, Daniel J.; Quicksall, Zachary S.; Patel, Tulsi A.; Carnwath, Troy P.; DeTure, Michael (2021-04-19). "Transcriptomic analysis to identify genes associated with selective hippocampal vulnerability in Alzheimer's disease". Nature Communications. 12 (1): 2311. Bibcode:2021NatCo..12.2311C. doi:10.1038/s41467-021-22399-3. ISSN 2041-1723. PMC 8055900 . PMID 33875655.
- ↑ Murray, Melissa E.; Moloney, Christina M.; Kouri, Naomi; Syrjanen, Jeremy A.; Matchett, Billie J.; Rothberg, Darren M.; Tranovich, Jessica F.; Sirmans, Tiffany N. Hicks; Wiste, Heather J.; Boon, Baayla D. C.; Nguyen, Aivi T.; Reichard, R. Ross; Dickson, Dennis W.; Lowe, Val J.; Dage, Jeffrey L. (2022-12-27). "Global neuropathologic severity of Alzheimer's disease and locus coeruleus vulnerability influences plasma phosphorylated tau levels". Molecular Neurodegeneration. 17 (1): 85. doi: 10.1186/s13024-022-00578-0 . ISSN 1750-1326. PMC 9795667 . PMID 36575455.
- ↑ De Widt, Lynda (19 May 2024). "Mayo Clinic researchers have discovered a series of brain changes characterized by unique clinical features and immune cell". Morning Sentinel ; Waterville, Maine– via Proquest.
- ↑ Bahrampour, Tara (2016-11-06). "Men may get Alzheimer's as often as women, we just haven't known how to spot it". The Daily Nonpareil. p. 49. Retrieved 2024-12-22.
- ↑ Hall, Melanie (2013-03-22). "Dreams can be a sign of dementia 30 years later". The Daily Telegraph. p. 3. Retrieved 2024-12-22.
- ↑ "ISTAART Neuroimaging PIA de Leon Award Winners" (PDF). Alzheimer's Association. 2023. Archived from the original (PDF) on 2024-08-07. Retrieved 2024-12-23.
- ↑ "Melissa Murray". The Pathologist. Retrieved 2024-12-23.
- ↑ Tommavongsa, Nicky (2022-12-16). "Melissa Murray, Ph.D., receives Mayo Clinic's 2022 Florida Investigator of the Year award". Mayo Clinic Alumni Association. Retrieved 2024-12-23.