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Handbook of Clinical Neurology 2018Senile plaques and neurofibrillary tangles are the principal histopathologic hallmarks of Alzheimer disease. The essential constituents of these lesions are structurally... (Review)
Review
Senile plaques and neurofibrillary tangles are the principal histopathologic hallmarks of Alzheimer disease. The essential constituents of these lesions are structurally abnormal variants of normally generated proteins: Aβ protein in plaques and tau protein in tangles. At the molecular level, both proteins in a pathogenic state share key properties with classic prions, i.e., they consist of alternatively folded, β-sheet-rich forms of the proteins that autopropagate by the seeded corruption and self-assembly of like proteins. Other similarities with prions include the ability to manifest as polymorphic and polyfunctional strains, resistance to chemical and enzymatic destruction, and the ability to spread within the brain and from the periphery to the brain. In Alzheimer disease, current evidence indicates that the pathogenic cascade follows from the endogenous, sequential corruption of Aβ and then tau. Therapeutic options include reducing the production or multimerization of the proteins, uncoupling the Aβ-tauopathy connection, or promoting the inactivation or removal of anomalous assemblies from the brain. Although aberrant Aβ appears to be the prime mover of Alzheimer disease pathogenesis, once set in motion by Aβ, the prion-like propagation of tauopathy may proceed independently of Aβ; if so, Aβ might be solely targeted as an early preventive measure, but optimal treatment of Alzheimer disease at later stages of the cascade could require intervention in both pathways.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Brain; Diagnosis, Differential; Humans; Prions
PubMed: 29887142
DOI: 10.1016/B978-0-444-63945-5.00016-7 -
Trends in Molecular Medicine Jun 2017Like many humans, non-human primates deposit copious misfolded Aβ protein in the brain as they age. Nevertheless, the complete behavioral and pathologic phenotype of... (Review)
Review
Like many humans, non-human primates deposit copious misfolded Aβ protein in the brain as they age. Nevertheless, the complete behavioral and pathologic phenotype of Alzheimer's disease, including Aβ plaques, neurofibrillary (tau) tangles, and dementia, has not yet been identified in a non-human species. Recent research suggests that the crucial link between Aβ aggregation and tauopathy is somehow disengaged in aged monkeys. Understanding why Alzheimer's disease fails to develop in species that are biologically proximal to humans could disclose new therapeutic targets in the chain of events leading to neurodegeneration and dementia.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Humans; Species Specificity
PubMed: 28483344
DOI: 10.1016/j.molmed.2017.04.001 -
The Journal of Clinical Psychiatry Aug 2022Diagnosing early-stage Alzheimer disease can lead to prompt initiation of treatment and slow down symptom progression. However, clinicians are not providing a diagnosis...
Diagnosing early-stage Alzheimer disease can lead to prompt initiation of treatment and slow down symptom progression. However, clinicians are not providing a diagnosis to over half of individuals who meet criteria for dementia. Tests for biomarkers, new symptomatic treatments and disease-modifying agents, and the addition of the preclinical stage to the diagnostic criteria for AD can aid in earlier disease recognition and developing treatment plans. Communicating diagnosis and information on next steps with patients and caregivers can lead to patient and caregiver involvement in decision-making and planning as well as participation in clinical trials and maximizing benefits and lifestyle interventions.
Topics: Alzheimer Disease; Caregivers; Humans
PubMed: 35921505
DOI: 10.4088/JCP.LI21019DH1C -
Revue Medicale Suisse Jan 2017
Topics: Alzheimer Disease; Humans; Practice Guidelines as Topic; Syndrome
PubMed: 28703970
DOI: No ID Found -
Current Neuropharmacology 2017Inflammation is a part of the first line of defense of the body against invasive pathogens, and plays a crucial role in tissue regeneration and repair. A proper... (Review)
Review
BACKGROUND
Inflammation is a part of the first line of defense of the body against invasive pathogens, and plays a crucial role in tissue regeneration and repair. A proper inflammatory response ensures the suitable resolution of inflammation and elimination of harmful stimuli, but when the inflammatory reactions are inappropriate it can lead to damage of the surrounding normal cells. The relationship between infections and Alzheimer's Disease (AD) etiology, especially lateonset AD (LOAD) has been continuously debated over the past three decades.
METHODS
This review discusses whether infections could be a causative factor that promotes the progression of AD and summarizes recent investigations associating infectious agents and chronic inflammation with AD. Preventive and therapeutic approaches to AD in the context of an infectious etiology of the disease are also discussed.
RESULTS
Emerging evidence supports the hypothesis of the role of neurotropic viruses from the Herpesviridae family, especially Human herpesvirus 1 (HHV-1), Cytomegalovirus (CMV), and Human herpesvirus 2 (HHV-2), in AD neuropathology. Recent investigations also indicate the association between Hepatitis C virus (HCV) infection and dementia. Among bacteria special attention is focused on spirochetes family and on periodontal pathogens such as Porphyromonas gingivalis or Treponema denticola that could cause chronic periodontitis and possibly contribute to the clinical onset of AD.
CONCLUSION
Chronic viral, bacterial and fungal infections might be causative factors for the inflammatory pathway in AD.
Topics: Alzheimer Disease; Animals; Communicable Diseases; Humans; Inflammation
PubMed: 28294067
DOI: 10.2174/1570159X15666170313122937 -
Mayo Clinic Proceedings Jun 2017Alzheimer disease (AD) was originally conceived as a rare disease that caused presenile dementia but has come to be understood as the most prevalent cause of dementia at... (Review)
Review
Alzheimer disease (AD) was originally conceived as a rare disease that caused presenile dementia but has come to be understood as the most prevalent cause of dementia at any age worldwide. It has an extended preclinical phase characterized by sequential changes in imaging and cerebrospinal fluid biomarkers with subtle memory decline beginning more than a decade before the emergence of symptomatic memory loss heralding the beginning of the mild cognitive impairment stage. The apolipoprotein E ε4 allele is a prevalent and potent risk factor for AD that has facilitated research into its preclinical phase. Cerebral Aβ levels build from preclinical through early dementia stages followed by hyperphosphorylated tau-related pathology, the latter driving cognitive deficits and dementia severity. Structural and molecular imaging can now recapitulate the neuropathology of AD antemortem. Autosomal dominant forms of early-onset familial AD gave rise to the amyloid hypothesis of AD, which, in turn, has led to therapeutic trials of immunotherapy designed to clear cerebral amyloid, but to date results have been disappointing. Genome-wide association studies have identified multiple additional risk factors, but to date none have yielded an effective alternate therapeutic target. Current and future trials aimed at presymptomatic individuals either harboring cerebral amyloid or at genetically high risk offer the hope that earlier intervention might yet succeed where trials in patients with established dementia have failed. A major looming challenge will be that of expensive, incompletely effective disease-modifying therapy: who and when to treat, and how to pay for it.
Topics: Aging; Alzheimer Disease; Apolipoproteins E; Brain; Humans; Magnetic Resonance Imaging
PubMed: 28578785
DOI: 10.1016/j.mayocp.2017.02.011 -
Protein & Cell Feb 2017Dementia is a comprehensive category of brain diseases that is great enough to affect a person's daily functioning. The most common type of dementia is Alzheimer's... (Review)
Review
Dementia is a comprehensive category of brain diseases that is great enough to affect a person's daily functioning. The most common type of dementia is Alzheimer's disease, which makes most of cases. New researches indicate that gastrointestinal tract microbiota are directly linked to dementia pathogenesis through triggering metabolic diseases and low-grade inflammation progress. A novel strategy is proposed for the management of these disorders and as an adjuvant for psychiatric treatment of dementia and other related diseases through modulation of the microbiota (e.g. with the use of probiotics).
Topics: Alzheimer Disease; Gastrointestinal Microbiome; Humans
PubMed: 27866330
DOI: 10.1007/s13238-016-0338-6 -
Journal of Alzheimer's Disease : JAD 2023Different investigations lead to the urgent need to generate validated clinical protocols as a tool for medical doctors to orientate patients under risk for a preventive... (Review)
Review
Different investigations lead to the urgent need to generate validated clinical protocols as a tool for medical doctors to orientate patients under risk for a preventive approach to control Alzheimer's disease. Moreover, there is consensus that the combined effects of risk factors for the disease can be modified according to lifestyle, thus controlling at least 40% of cases. The other fraction of cases are derived from candidate genes and epigenetic components as a relevant factor in AD pathogenesis. At this point, it appears to be of critical relevance the search for molecular biomarkers that may provide information on probable pathological events and alert about early detectable risks to prevent symptomatic events of the disease. These precocious detection markers will then allow early interventions of non-symptomatic subjects at risk. Here, we summarize the status and potential avenues of prevention and highlight the usefulness of biological and reliable markers for AD.
Topics: Humans; Alzheimer Disease; Biomarkers; Life Style; Risk Factors; tau Proteins
PubMed: 37807781
DOI: 10.3233/JAD-230454 -
Turkish Journal of Medical Sciences 2015Alzheimer disease (AD) is one of the most common neurodegenerative diseases and the most prevalent form of dementia. Some factors in the development of AD, age being the... (Review)
Review
Alzheimer disease (AD) is one of the most common neurodegenerative diseases and the most prevalent form of dementia. Some factors in the development of AD, age being the best-known one, have been suggested; however, no causes have been found yet. The pathophysiology of the disease is highly complex, current therapies are palliative, and a cure is still lacking. Adverse effects of anesthetics in the elderly have been reported since the 1950s; however, awareness of this old problem has recently gained inportance again. Whether exposure to surgery and general anesthesia (GA) is associated with the development of AD has been questioned. As the population is aging, many elderly patients will need to be anesthetized, and maybe some were already anesthetized before they were diagnosed. Exposure to anesthetics has been demonstrated to promote pathogenesis of AD in both in vitro and in vivo studies. However, to date, there have not been any clinical trials to address a link between exposure to GA and the development of AD in humans. Therefore, before making any conclusions we need further studies, but we should be aware of the potential risks and take cautions with vulnerable elderly patients.
Topics: Alzheimer Disease; Anesthesia, General; Anesthetics, General; Cognition; Humans; Postoperative Complications; Risk Factors
PubMed: 26738343
DOI: No ID Found -
FP Essentials May 2018Alzheimer disease (AD) occurs in 8.8% of older US adults and is the sixth leading cause of death among older adults. Medicare annual wellness visits require screening... (Review)
Review
Alzheimer disease (AD) occurs in 8.8% of older US adults and is the sixth leading cause of death among older adults. Medicare annual wellness visits require screening for cognitive impairment but do not specify screening methods. Numerous screening instruments are available. If results are positive, evaluation with well-validated assessment tools is needed. If cognitive impairment is confirmed, laboratory tests and imaging studies should be obtained to rule out reversible etiologies. If patients meet diagnostic criteria for AD, clinicians should educate patients and families on the expected course and help them complete advance directives. Nutrition, behavioral issues, patient safety issues, and physical activity should be addressed. Physicians should screen for and manage concomitant depression. Troublesome behaviors should be managed with nonpharmacotherapeutic measures first. Pain should be considered as a possible cause of behavior. Antipsychotics should be reserved for select cases in which safety is an issue. Drugs for improving cognition can be prescribed but these typically result in short-term improvements and do not prevent disease progression. These drugs should be discontinued if adverse effects occur or when dementia worsens. Research on anti-amyloid and anti-tau protein drugs is promising but has not yet led to useful breakthroughs.
Topics: Aged; Alzheimer Disease; Geriatric Assessment; Humans; Mass Screening; Medicare; United States
PubMed: 29714994
DOI: No ID Found