Review
Cell Biology
Patrizia Mecocci, Virginia Boccardi
Summary: This passage challenges the traditional view that amyloid is the leading cause of AD, proposing instead that the progressive decline in brain energy levels during aging is the main risk factor for dementia in older individuals. It suggests that optimizing brain energetics should be a key component in future strategies for preventing and treating dementia.
AGEING RESEARCH REVIEWS
(2021)
Article
Biochemistry & Molecular Biology
Mar Cuadrado-Tejedor, Marta Perez-Gonzalez, Rocio Alfaro-Ruiz, Sara Badesso, Diego Sucunza, Maria Espelosin, Susana Ursua, Mercedes Lachen-Montes, Joaquin Fernandez-Irigoyen, Enrique Santamaria, Rafael Lujan, Ana Garcia-Osta
Summary: The study found that overexpression of hTauP301L in APP/PS1 transgenic mice accelerates memory deficits and induces tau aggregation, but does not affect memory function in wild type mice. The presence of amyloid is necessary to induce tau aggregation, leading to tau accumulation in dendritic mitochondria which may alter synapse function and contribute to accelerated cognitive decline in APP/PS1 mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, General & Internal
Xiaolei Han, Chaoqun Wang, Lin Song, Xiaojie Wang, Shi Tang, Tingting Hou, Cuicui Liu, Xiaoyan Liang, Chengxuan Qiu, Yongxiang Wang, Yifeng Du
Summary: Previous research has revealed that KIBRA regulates the secretion of extracellular vesicles (EVs), which play a crucial role in amyloid beta (Aβ) metabolism. This study further demonstrates that KIBRA controls Aβ metabolism by regulating the secretion of APP-CTF β/Aβ-associated EVs. Whole exon sequencing also identifies the association of KIBRA rs28421695 polymorphism with plasma Aβ levels.
Article
Neurosciences
Joseph R. Winer, Allison Morehouse, Laura Fenton, Theresa M. Harrison, Lylian Ayangma, Mark Reed, Samika Kumar, Suzanne L. Baker, William J. Jagust, Matthew P. Walker
Summary: This study found that early-stage tau and Aβ deposition in Alzheimer's disease can impact sleep, with tau burden leading to worse objective sleep and Aβ burden associated with decreased self-reported sleep quality. Aβ deposition also predicts a mismatch between objective and subjective sleep evaluation, with individuals underestimating their sleep, which is further linked to worse executive function.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Tatsuhiro Ayabe, Chika Takahashi, Rena Ohya, Yasuhisa Ano
Summary: Beta-lactolin improves mitochondrial functions and prevents neuronal cell death in Alzheimer's disease-related neuronal cell models, demonstrating its advantage in maintaining neuronal health.
Article
Geriatrics & Gerontology
Irene Costa-Laparra, Elena Juarez-Escoto, Carlos Vicario, Rosario Moratalla, Patricia Garcia-Sanz
Summary: Alzheimer's disease is characterized by memory loss and the presence of senile plaques and neurofibrillary tangles. This study investigates the impact of APOE ε4 and G206D-PSEN1 on the underlying mechanisms of Alzheimer's disease, including autophagy pathway and mitochondrial dysfunction.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Review
Neurosciences
Heather M. Wilkins, Russell H. Swerdlow
Summary: Advancing age is a major risk factor for Alzheimer's disease. The relationship between aging and AD is complex and requires further research to definitively understand.
TRANSLATIONAL NEURODEGENERATION
(2021)
Review
Biochemistry & Molecular Biology
Zdenek Fisar
Summary: Damage or loss of brain cells and impaired neurochemistry, neurogenesis, and synaptic and nonsynaptic plasticity of the brain lead to dementia in neurodegenerative diseases, such as Alzheimer's disease (AD). Injury to synapses and neurons and accumulation of extracellular amyloid plaques and intracellular neurofibrillary tangles are considered the main morphological and neuropathological features of AD. Age, genetic and epigenetic factors, environmental stressors, and lifestyle contribute to the risk of AD onset and progression. These risk factors are associated with structural and functional changes in the brain, leading to cognitive decline. Biomarkers of AD reflect or cause specific changes in brain function, especially changes in pathways associated with neurotransmission, neuroinflammation, bioenergetics, apoptosis, and oxidative and nitrosative stress. Even in the initial stages, AD is associated with A beta neurotoxicity, mitochondrial dysfunction, and tau neurotoxicity. The integrative amyloid-tau-mitochondrial hypothesis assumes that the primary cause of AD is the neurotoxicity of A beta oligomers and tau oligomers, mitochondrial dysfunction, and their mutual synergy. For the development of new efficient AD drugs, targeting the elimination of neurotoxicity, mutual potentiation of effects, and unwanted protein interactions of risk factors and biomarkers (mainly A beta oligomers, tau oligomers, and mitochondrial dysfunction) in the early stage of the disease seems promising.
Review
Cell Biology
Dipen Rajgor, Theresa M. Welle, Katharine R. Smith
Summary: Neurons exhibit a high degree of compartmentalization, with localized protein synthesis at synaptic sites being essential for synaptic plasticity. Coordinated mechanisms involving RNA trafficking and mitochondrial fueling of synaptic translation are crucial for regulating activity-dependent protein synthesis and modulating synaptic strength.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Thibault Courtellemont, Maria Giovanna De Leo, Navin Gopaldass, Andreas Mayer
Summary: Endo-lysosomal compartments exchange proteins through different processes, including fusion, fission, and endosomal transport carriers. The membrane fission events that occur during these processes are not well understood. This study identifies the CROP complex as a factor that plays a role in membrane fission. The CROP complex consists of members from two protein families and enhances the membrane fission activity of a specific protein. Disrupting the CROP complex prevents fragmentation of lysosome-like structures in yeast and impairs cargo export in mammalian endosomes.
Review
Biochemistry & Molecular Biology
Ujala Sehar, Priyanka Rawat, Arubala P. Reddy, Jonathan Kopel, P. Hemachandra Reddy
Summary: Alzheimer's disease is a progressive neurodegenerative disease that affects behavior, thinking, and memory in elderly individuals. It can occur in two forms – early onset familial and late-onset sporadic, with genetic mutations and lifestyle/environment factors playing a role in its development. Key pathological changes include the production and accumulation of Aβ and p-tau in affected brain regions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Jenna N. Adams, Theresa M. Harrison, Anne Maass, Suzanne L. Baker, William J. Jagust
Summary: This study aimed to investigate the mechanisms underlying the initial accumulation of tau pathology and the predictive roles of age, AP, and neural activity in tau accumulation. The results showed that older age, higher neural activity, and higher baseline EC tau levels were associated with tau accumulation. Additionally, AP facilitated the spread of tau.
JOURNAL OF NEUROSCIENCE
(2022)
Review
Neurosciences
Saffire H. Krance, Che-Yuan Wu, Alison C. Y. Chan, Stephanie Kwong, Bing Xin Song, Lisa Y. Xiong, Michael Ouk, Ming Hui Chen, Jane Zhang, Adrian Yung, Meagan Stanley, Nathan Herrmann, Krista L. Lanctot, Walter Swardfager
Summary: Differences in endosomal-lysosomal and autophagy proteins were observed in the cerebrospinal fluid (CSF) of individuals with Alzheimer's disease compared to healthy controls. This suggests that dysregulation of these proteins may play a role in the pathogenesis of Alzheimer's disease.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Review
Pharmacology & Pharmacy
Benjamin R. Troutwine, Laylan Hamid, Colton R. Lysaker, Taylor A. Strope, Heather M. Wilkins
Summary: Genetic variation in the APOE gene is associated with the risk of Alzheimer's disease. The APOE epsilon 4 alleles are the strongest genetic risk factor for late onset sporadic AD, while the APOE epsilon 2 alleles have lower risk and the APOE epsilon 3 alleles have neutral risk.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Cell Biology
Shuqi Du, Feng Jin, Laure Maneix, Manasee Gedam, Yin Xu, Andre Catic, Meng C. Wang, Hui Zheng
Summary: This study reveals a specific regulation of FoxO3 in the CNS, showing reduced levels in the cortex of aged mice but not in the hippocampus. FoxO3 responds to insulin/AKT signaling in astrocytes and plays a role in astrocyte activity and lipid metabolism. Loss of FoxO3 leads to cortical astrogliosis, altered lipid metabolism, and impaired A beta uptake, indicating a protective role of astroglial FoxO3 against brain aging and AD.
