Pathophysiology of Alzheimer’s disease

2017 ◽  
Author(s):  
Shelley J. Allen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Essential Role ◽  
Amyloid Plaques ◽  
Early Screening ◽  
Risk Genes ◽  
Risk Gene ◽  
Sporadic Cases ◽  
Synaptic Changes

We now know that the onset of the pathological processes leading to Alzheimer’s disease (AD) may be 15–20 years before symptoms appear. This focuses attention on synaptic changes and the early role of tau, and less on the hallmark amyloid plaques (Aβ‎) and neurofibrillary tau tangles. Sensitive biomarkers to allow early screening will be essential. Familial autosomal AD is the result of mutations in one of three genes (APP, PSEN1, or PSEN2), each directly related to increased Aβ‎, and informs pathological mechanisms in common sporadic cases, but are also subject to influence by many risk genes and environmental factors. The essential role of apolipoprotein E in neuronal repair and Aβ‎ clearance provides a therapeutic target but also a challenge in carriers of the risk gene APOE4. Current treatments are symptomatic, derived from neurotransmitter deficits seen; particularly cholinergic, but emerging data suggest alternative targets which may prove more productive.

scholarly journals Modeling of Tau-Mediated Synaptic and Neuronal Degeneration in Alzheimer's Disease

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Tomasz Jaworski ◽  
Sebastian Kügler ◽  
Fred Van Leuven
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuronal Degeneration ◽  
Neuronal Loss ◽  
Amyloid Plaques ◽  
Amyloid Peptides ◽  
Alois Alzheimer ◽  
Second Shift ◽  
Amyloid Cascade

Patients suffering from Alzheimer's disease (AD) are typified and diagnosed postmortem by the combined accumulations of extracellular amyloid plaques and of intracellular tauopathy, consisting of neuropil treads and neurofibrillary tangles in the somata. Both hallmarks are inseparable and remain diagnostic as described by Alois Alzheimer more than a century ago. Nevertheless, these pathological features are largely abandoned as being the actual pathogenic or neurotoxic factors. The previous, almost exclusive experimental attention on amyloid has shifted over the last 10 years in two directions. Firstly, from the “concrete” deposits of amyloid plaques to less well-defined soluble or pseudosoluble oligomers of the amyloid peptides, ranging from dimers to dodecamers and even larger aggregates. A second shift in research focus is from amyloid to tauopathy, and to their mutual relation. The role of Tau in the pathogenesis and disease progression is appreciated as leading to synaptic and neuronal loss, causing cognitive deficits and dementia. Both trends are incorporated in a modified amyloid cascade hypothesis, briefly discussed in this paper that is mainly concerned with the second aspect, that is, protein Tau and its associated fundamental questions.

scholarly journals The role of Alzheimer's disease risk genes in endolysosomal pathways

2022 ◽  
Vol 162 ◽  
pp. 105576
Author(s):  
Marcell P. Szabo ◽  
Swati Mishra ◽  
Allison Knupp ◽  
Jessica E. Young
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Risk ◽  
Risk Genes

Environmental and Genetic Risk Factors for Alzheimer's Disease in Spain

2009 ◽  
Vol 4 (2) ◽  
pp. 125 ◽  
Author(s):  
Israel Ampuero ◽  
Félix Bermejo-Pareja ◽  
Guillermo García Ribas ◽  
◽  
◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Risk ◽  
Neurodegenerative Disorder ◽  
Genetic Risk Factors ◽  
Unknown Aetiology ◽  
Future Studies ◽  
Sporadic Cases

Alzheimer's disease is a complex neurodegenerative disorder of unknown aetiology, and an important number of cases are sporadic. To date, only some of the genetic and environmental risk factors for Alzheimer's disease have been identified. It is very important to understand the role of environmental and genetic risk factors in Alzheimer's disease in order to develop therapeutic strategies. For sporadic cases of Alzheimer's disease, many environmental and genetic risk factor modifiers have been described, but – with a few exceptions – most of them remain controversial. In this article we review some studies of these risk factors in a Spanish population to identify a few directives for future studies.

P1-143: Investigating the Role of BIN1 , an Alzheimer's Disease Risk Gene, in Endocytosis at the Blood-Brain Barrier

2016 ◽  
Vol 12 ◽  
pp. P457-P458
Author(s):  
Anna L. Burt ◽  
Rhian S. Thomas ◽  
Melanie L. Dunstan ◽  
Rebecca Sims ◽  
Julie Williams
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Disease Risk ◽  
Brain Barrier ◽  
Risk Gene ◽  
Blood Brain

The Essential Role of Soluble Aβ Oligomers in Alzheimer’s Disease

2015 ◽  
Vol 53 (3) ◽  
pp. 1905-1924 ◽  
Author(s):  
Zi-Xuan Wang ◽  
Lan Tan ◽  
Jinyuan Liu ◽  
Jin-Tai Yu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Essential Role ◽  
Aβ Oligomers ◽  
Soluble Aβ Oligomers

scholarly journals Therapeutic Potential of Neu1 in Alzheimer’s Disease Via the Immune System

2021 ◽  
Vol 36 ◽  
pp. 153331752199614
Author(s):  
Aiza Khan ◽  
Sumit Das ◽  
Consolato Sergi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune System ◽  
Therapeutic Potential ◽  
Amyloid Plaques ◽  
Beta Amyloid ◽  
Underlying Mechanism ◽  
Amyloid Deposits ◽  
Potential Therapeutic Role

Alzheimer’s Disease (AD) is pathologically characterized by the accumulation of soluble oligomers causing extracellular beta-amyloid deposits in form of neuritic plaques and tau-containing intraneuronal neurofibrillary tangles in brain. One proposed mechanism explaining the formation of these proteins is impaired phagocytosis by microglia/macrophages resulting in defective clearance of soluble oligomers of beta-amyloid stimulating aggregation of amyloid plaques subsequently causing AD. However, research indicates that activating macrophages in M2 state may reduce toxic oligomers. NEU1 mutation is associated with a rare disease, sialidosis. NEU1 deficiency may also cause AD-like amyloidogenic process. Amyloid plaques have successfully been reduced using NEU1.Thus, NEU1 is suggested to have therapeutic potential for AD, with lysosomal exocytosis being suggested as underlying mechanism. Studies however demonstrate that NEU1 may activate macrophages in M2 state, which as noted earlier, is crucial to reducing toxic oligomers. In this review, authors discuss the potential therapeutic role of NEU1 in AD via immune system.

The essential role of lipids in Alzheimer's disease

Biochimie ◽  
2009 ◽  
Vol 91 (6) ◽  
pp. 804-809 ◽  
Author(s):  
Sabrina Florent-Béchard ◽  
Cédric Desbène ◽  
Pierre Garcia ◽  
Ahmad Allouche ◽  
Ihsen Youssef ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Essential Role

scholarly journals The Role of Butyrylcholinesterase and Iron in the Regulation of Cholinergic Network and Cognitive Dysfunction in Alzheimer’s Disease Pathogenesis

2021 ◽  
Vol 22 (4) ◽  
pp. 2033
Author(s):  
Jacek Jasiecki ◽  
Monika Targońska ◽  
Bartosz Wasąg
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Iron Homeostasis ◽  
Clinical Signs ◽  
Amyloid Β ◽  
Amyloid Plaques ◽  
Postmortem Brain ◽  
Brain Iron ◽  
Brain Functions

Alzheimer’s disease (AD), the most common form of dementia in elderly individuals, is marked by progressive neuron loss. Despite more than 100 years of research on AD, there is still no treatment to cure or prevent the disease. High levels of amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs) in the brain are neuropathological hallmarks of AD. However, based on postmortem analyses, up to 44% of individuals have been shown to have high Aβ deposits with no clinical signs, due to having a “cognitive reserve”. The biochemical mechanism explaining the prevention of cognitive impairment in the presence of Aβ plaques is still unknown. It seems that in addition to protein aggregation, neuroinflammatory changes associated with aging are present in AD brains that are correlated with a higher level of brain iron and oxidative stress. It has been shown that iron accumulates around amyloid plaques in AD mouse models and postmortem brain tissues of AD patients. Iron is required for essential brain functions, including oxidative metabolism, myelination, and neurotransmitter synthesis. However, an imbalance in brain iron homeostasis caused by aging underlies many neurodegenerative diseases. It has been proposed that high iron levels trigger an avalanche of events that push the progress of the disease, accelerating cognitive decline. Patients with increased amyloid plaques and iron are highly likely to develop dementia. Our observations indicate that the butyrylcholinesterase (BChE) level seems to be iron-dependent, and reports show that BChE produced by reactive astrocytes can make cognitive functions worse by accelerating the decay of acetylcholine in aging brains. Why, even when there is a genetic risk, do symptoms of the disease appear after many years? Here, we discuss the relationship between genetic factors, age-dependent iron tissue accumulation, and inflammation, focusing on AD.

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