Article
Biochemistry & Molecular Biology
Rhett J. Britton, James M. Hutchison, Charles R. Sanders
Summary: In Alzheimer's disease (AD) research, the proteins of interest are amyloid precursor protein (APP) and tau, which play crucial roles in the disease mechanism. The relationship between A beta and tau pathologies remains unclear, with studies suggesting that A beta may induce or enhance tau protein formation in neurofibrillary tangles.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Review
Geriatrics & Gerontology
Jiang Chen, Jun-Sheng Chen, Song Li, Fengning Zhang, Jie Deng, Ling-Hui Zeng, Jun Tan
Summary: Decades of research have shown that amyloid-beta (Aβ) plays an undeniable role in the development of Alzheimer's disease (AD). However, the focus on the pathological effects of Aβ may overshadow the significance of its metabolic precursor, amyloid precursor protein (APP), in the occurrence and progression of AD. This review explores the various roles of APP in AD, including its structure, functions, enzymatic processing, and potential therapeutic approaches to targeting APP to ameliorate AD pathologies and halt disease progression.
Article
Geriatrics & Gerontology
Jacob W. Astroski, Leonora K. Akporyoe, Elliot J. Androphy, Sara K. Custer
Summary: Understanding the genetics of families with histories of AD is crucial in understanding the cellular processes involved in Alzheimer's disease. Mutations in the COPI complex have been found in these families, and recent studies suggest that components of the COPI complex can affect the metabolism of pathogenic AD proteins. Depletion of the COPI subunit a-COP has been shown to alter the processing of both APP and Tau, potentially leading to pathogenic changes associated with AD.
NEUROBIOLOGY OF AGING
(2021)
Article
Clinical Neurology
Julia Schumacher, Jeffrey L. Gunter, Scott A. Przybelski, David T. Jones, Jonathan Graff-Radford, Rodolfo Savica, Christopher G. Schwarz, Matthew L. Senjem, Clifford R. Jack, Val J. Lowe, David S. Knopman, Julie A. Fields, Walter K. Kremers, Ronald C. Petersen, Neill R. Graff-Radford, Tanis J. Ferman, Bradley F. Boeve, Alan J. Thomas, John-Paul Taylor, Kejal Kantarci
Summary: The presence of concurrent Alzheimer's disease pathology in patients with DLB is associated with more severe loss of default mode network connectivity. Additionally, higher functional connectivity between brain regions is related to higher tau pathology levels in cognitively normal, Alzheimer's disease, and DLB patients.
Correction
Clinical Neurology
Woo Shik Shin, Jing Di, Qin Cao, Binsen Li, Paul M. Seidler, Kevin A. Murray, Gal Bitan, Lin Jiang
Summary: The paper has been amended and the updated version can be accessed through the original article.
ALZHEIMERS RESEARCH & THERAPY
(2021)
Article
Geriatrics & Gerontology
Elijah Mak, Nicolas Nicastro, Maura Malpetti, George Savulich, Ajenthan Surendranathan, Negin Holland, Luca Passamonti, P. Simon Jones, Stephen F. Carter, Li Su, Young T. Hong, Tim D. Fryer, Guy B. Williams, Franklin Aigbirhio, James B. Rowe, John T. O'Brien
Summary: The study examined the distribution of tau burden in patients with DLB and AD, revealing a lower tau deposition in DLB patients compared to AD patients. The findings suggest that tau may interact synergistically with other pathologic processes to aggravate disease severity in DLB, as indicated by its associations with cognitive impairment.
NEUROBIOLOGY OF AGING
(2021)
Article
Neurosciences
Giulia Puliatti, Domenica Donatella Li Puma, Giuseppe Aceto, Giacomo Lazzarino, Erica Acquarone, Renata Mangione, Luciano 'Adamio, Cristian Ripoli, Ottavio Arancio, Roberto Piacentini, Claudio Grassi
Summary: Our study found that the specific antibody anti-glypican 4 (GPC4) significantly reduced the uptake of extracellular tau oligomers (oTau) by astrocytes and prevented oTau-induced alterations in calcium-dependent gliotransmitter release. Furthermore, GPC4 expression was found to be APP/AICD-dependent and mediated the accumulation of oTau in astrocytes, resulting in synaptotoxic effects.
PROGRESS IN NEUROBIOLOGY
(2023)
Article
Neurosciences
Roaa H. Alalwany, Tom Hawtrey, Kevin Morgan, Jonathan C. Morris, Lucy F. Donaldson, David O. Bates
Summary: Alzheimer's disease (AD) is characterized by memory decline and cognitive impairment caused by neuritic plaques and neurofibrillary tangles. The study explores the potential neuroprotective effects of different VEGF splice variants and splicing factor kinase inhibitors. VEGF-A(165)a enhances neurite outgrowth, while VEGF-A(165)b prevents neurite dieback in a tau hyperphosphorylation model. Inhibition of SRPK1 protects against neurite dieback by promoting VEGF-A(165)b isoform expression. The findings suggest therapeutic potential in AD by controlling isoform activities based on the predominant neurotoxicity mechanism - tau or β-amyloid.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Clinical Neurology
Patricia Diaz-Galvan, Scott A. Przybelski, Timothy G. Lesnick, Christopher G. Schwarz, Matthew L. Senjem, Jeffrey L. Gunter, Clifford R. Jack, Hoon-Ki Paul Min, Manoj Jain, Toji Miyagawa, Leah K. Forsberg, Julie A. Fields, Rodolfo Savica, Jonathan Graff-Radford, David T. Jones, Hugo Botha, Erik K. St Louis, David S. Knopman, Vijay K. Ramanan, Owen Ross, Neill Graff-Radford, Gregory S. Day, Dennis W. Dickson, Tanis J. Ferman, Ronald C. Petersen, Val J. Lowe, Brad F. Boeve, Kejal Kantarci
Summary: Aβ load increases throughout the DLB continuum, with significant elevation in the prodromal stage of MCI-LB and in DLB. APOE ε4 carriers have higher Aβ levels compared to noncarriers in MCI-LB and DLB groups. Women tend to have higher Aβ levels than men as they get older.
Article
Pharmacology & Pharmacy
Tong Zhang, Jiafeng Yu, Gang Wang, Runhe Zhang
Summary: The study revealed that TNFRSF21 binds with APP to regulate neural inflammatory effects in AD. Inhibiting TNFRSF21 can reduce APP expression and decrease neuroinflammation, making it a potential target for treating AD.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Antonio J. Figueira, Guilherme G. Moreira, Joana Saavedra, Isabel Cardoso, Claudio M. Gomes
Summary: The hallmark of Alzheimer's disease (AD) includes the aggregation of amyloid-beta (A beta), tau, and neuroinflammation. In this study, the researchers found that S100B protein, which is upregulated in AD, can inhibit the aggregation of A beta 42, and this activity is dependent on Ca2+ binding. They also discovered that S100B exists in tetrameric form, and tetrameric S100B is more effective in inhibiting A beta 42 aggregation. These findings highlight the importance of S100B protein in regulating AD proteotoxicity.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Clinical Neurology
Anika Wuestefeld, Alexa Pichet Binette, David van Berron, Nicola Spotorno, Danielle van Westen, Erik Stomrud, Niklas Mattsson-Carlgren, Olof Strandberg, Ruben Smith, Sebastian Palmqvist, Trevor Glenn, Svenja Moes, Michael Honer, Konstantinos Arfanakis, Lisa L. Barnes, David A. Bennett, Julie A. Schneider, Laura E. M. Wisse, Oskar Hansson
Summary: This study found that tau pathology, independent of amyloid-beta, may exist outside of the medial temporal lobe and affect cognition and brain structures. These findings have implications for understanding the spread of tau in Alzheimer's disease and suggest the potential use of tau-targeting treatments.
Article
Neurosciences
Alexandra A. Sandberg, Evan Manning, Heather M. Wilkins, Randall Mazzarino, Taylor Minckley, Russell H. Swerdlow, David Patterson, Yan Qin, Daniel A. Linseman
Summary: In this study, the potential of mitochondrial-targeted AICD to induce neuronal apoptosis and its mechanism of neurotoxicity were examined. The results showed that only when AICD was targeted to the mitochondria, significant neuronal apoptosis was induced. Furthermore, AICD induced apoptosis via a mechanism that is distinct from that of A beta.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Ruth Maron, Yaron Vinik, Michael Tsoory, Meir Wilchek, Ruth Arnon
Summary: This study finds that the major proteins involved in Alzheimer's disease are amyloid precursor protein (APP) and Tau. It demonstrates that connecting the peptides APP1 (390-412) and Tau1 (19-34) with either a flexible or a rigid peptide bridge can inhibit the interaction between APP and Tau proteins in vitro. Moreover, in vivo studies in transgenic mice show that nasal administration of the flexible linked peptide reduces amyloid plaque burden and prevents cognitive deterioration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Bhumsoo Kim, Yoon-Tae Kang, Faye E. Mendelson, John M. Hayes, Masha G. Savelieff, Sunitha Nagrath, Eva L. Feldman
Summary: The metabolic syndrome (MetS) and Alzheimer's disease share various pathological features, including insulin resistance, abnormal protein processing, mitochondrial dysfunction, inflammation, and oxidative stress. This study demonstrates that palmitate and high glucose induce insulin resistance and amyloid precursor protein phosphorylation in brain cells, and these effects are mediated by extracellular vesicles (EVs). Furthermore, EVs derived from palmitate-treated brain cells enhance insulin resistance in recipient neurons. These findings suggest a novel mechanism underlying the increased risk of Alzheimer's disease in individuals with MetS, implicating EVs in the spread of Alzheimer's pathology and insulin resistance.
JOURNAL OF EXTRACELLULAR VESICLES
(2023)