Article
Clinical Neurology
David C. Hondius, Frank Koopmans, Conny Leistner, Debora Pita-Illobre, Regina M. Peferoen-Baert, Fenna Marbus, Iryna Paliukhovich, Ka Wan Li, Annemieke J. M. Rozemuller, Jeroen J. M. Hoozemans, August B. Smit
Summary: This study provides a comprehensive assessment of protein abundances in neurons with granulovacuolar degeneration (GVD) and those bearing neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) patients. The research revealed significant changes in protein composition in GVD and tangle-bearing neurons, with proteins related to protein folding, proteasomal function, endolysosomal pathway, and microtubule function being affected in GVD neurons. The study suggests that GVD is part of a pre-NFT stage in AD pathogenesis and may disrupt proteostasis and cellular homeostasis.
ACTA NEUROPATHOLOGICA
(2021)
Review
Immunology
Minghui Wang, Hu Zhang, Jiling Liang, Jielun Huang, Ning Chen
Summary: Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by the formation of neurofibrillary tangles and senile plaques. Neuroinflammation, specifically the long-term activation of pro-inflammatory microglia and NLRP3 inflammasomes, plays a crucial role in the development and progression of AD. Exercise has been found to ameliorate AD by regulating the immune response and promoting neurogenesis in the hippocampus.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Clinical Neurology
Christina M. Moloney, Sydney A. Labuzan, Julia E. Crook, Habeeba Siddiqui, Monica Castanedes-Casey, Christian Lachner, Ronald C. Petersen, Ranjan Duara, Neill R. Graff-Radford, Dennis W. Dickson, Michelle M. Mielke, Melissa E. Murray
Summary: This study aims to characterize the recognition of phosphorylated tau sites in early neurofibrillary tangle maturity levels, which may explain why these fluid biomarkers can be observed before symptom onset.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Jamie M. Walker, William Goette, Kurt Farrell, Megan A. Iida, Esma Karlovich, Charles F. White III, John E. Crary, Timothy Richardson
Summary: The distribution and spread of neurofibrillary degeneration in Alzheimer's disease (AD) and primary age-related tauopathy (PART) are influenced by the presence and extent of amyloid beta (Aβ) burden in the entorhinal cortex and CA1 subregion of the hippocampus. However, there is an early selective vulnerability of the CA2 subregion in PART, which is not correlated with Aβ burden.
ALZHEIMERS & DEMENTIA
(2023)
Review
Pharmacology & Pharmacy
Zhikun Shi, Hongyu Chen, Xu Zhou, Wei Yang, Yang Lin
Summary: Ginsenosides, the most important pharmacological active ingredient of ginseng, have shown potential in inhibiting the pathogenesis of AD. This review analyzes the mechanisms of ginsenosides in inhibiting the deposition of Aβ and NFTs, as well as their neuroprotective effects through antioxidant, anti-inflammatory, and anti-apoptosis mechanisms. Furthermore, the delivery route and mode of ginsenosides are discussed, providing a deeper understanding of their clinical application in AD treatment.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Neurosciences
Gabriel A. Marx, Daniel G. Koenigsberg, Andrew T. McKenzie, Justin Kauffman, Russell W. Hanson, Kristen Whitney, Maxim Signaevsky, Marcel Prastawa, Megan A. Iida, Charles L. White, Jamie M. Walker, Timothy E. Richardson, John Koll, Gerardo Fernandez, Jack Zeineh, Carlos Cordon-Cardo, John F. Crary, Kurt Farrell
Summary: Tauopathies are neurodegenerative diseases characterized by abnormal tau protein-containing neurofibrillary tangles (NFTs). This study utilized an AI-based method to quantitatively analyze tau pathology and found that AI-derived NFT metrics significantly predicted cognitive impairment in PART patients.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Clinical Neurology
M. -Marsel Mesulam, Christina A. Coventry, Eileen H. Bigio, Jaiashre Sridhar, Nathan Gill, Angela J. Fought, Hui Zhang, Cynthia K. Thompson, Changiz Geula, Tamar Gefen, Margaret Flanagan, Qinwen Mao, Sandra Weintraub, Emily J. Rogalski
Summary: Primary progressive aphasia is a neurodegenerative disease that selectively impairs language function. Autopsies and longitudinal studies have shown that primary progressive aphasia has various neuropathological changes, with Alzheimer's disease being the most common. Different variants of primary progressive aphasia have distinct neuropathological correlates, and word comprehension impairments are strong predictors of underlying neuropathology. Different types of primary progressive aphasia have different patterns of cortical atrophy, but all show severe damage to the left hemisphere language network. This study is important for understanding the neuropathological and clinical differences in primary progressive aphasia.
Review
Neurosciences
Tomas Kavanagh, Aditi Halder, Eleanor Drummond
Summary: Pathological tau aggregation is a key feature of many neurodegenerative diseases, but varies widely in affected brain regions, symptoms, morphology, conformation, and isoform ratio. Tau interactome studies provide important insights into disease mechanisms and cellular environment during tau aggregation. Analysis of 12 tau interactome studies revealed consistent interactions with proteins involved in RNA binding, ribosome, and proteasome function, with differences observed between human and rodent studies. Dysregulation of tau interactions was observed during the development of pathology, suggesting a role for RNA binding proteins in driving tau pathology.
MOLECULAR NEURODEGENERATION
(2022)
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)
Review
Biochemistry & Molecular Biology
Moxin Wu, Zhiying Chen, Min Jiang, Bing Bao, Dongling Li, Xiaoping Yin, Xueren Wang, Dan Liu, Ling-Qiang Zhu
Summary: Neuronal death is a common hallmark of neurological diseases, with tau playing a key role in various regulatory pathways. Pathological tau is associated with irreversible neuronal death in different forms, but it can also have protective effects. Understanding the dual role of pathological tau in neuronal death is crucial for developing targeted therapies for neurological disorders.
MOLECULAR PSYCHIATRY
(2023)
Article
Clinical Neurology
John L. Robinson, Sharon X. Xie, Daniel R. Baer, EunRan Suh, Vivianna M. Van Deerlin, Nicholas J. Loh, David J. Irwin, Corey T. McMillan, David A. Wolk, Alice Chen-Plotkin, Daniel Weintraub, Theresa Schuck, Virginia M. Y. Lee, John Q. Trojanowski, Edward B. Lee
Summary: In this retrospective study, the incidence of 10 pathologies in neurodegenerative disease (ND) and normal aging was examined, with up to seven pathologies observed concurrently resulting in 161 different combinations. The presence of multiple additive pathologies was associated with factors such as longer disease duration, clinical dementia, older age, and APOE e4 status.
Article
Biochemistry & Molecular Biology
Lea Langer Horvat, Ena Spanic Popovacki, Mirjana Babic Leko, Klara Zubcic, Luka Horvat, Maja Mustapic, Patrick R. Hof, Goran Simic
Summary: The study found that both human tau oligomers and tau fibrils can rapidly propagate and induce tau-related changes, but with some differences in the spreading pattern and regions. Rats injected with human tau fibrils showed more severe tau protein changes after 4 months, which correlated well with cognitive impairment.
Article
Clinical Neurology
Ji-Hye L. Hwang, Olga S. Perloff, Stephanie E. Gaus, Camila Benitez, Carolina Alquezar, Celica Q. Cosme, Alissa L. Nana, Sarat C. Vatsavayai, Eliana M. Ramos, Daniel H. Geschwind, Bruce L. Miller, Aimee W. Kao, William W. Seeley
Summary: This study found that individuals with tuberous sclerosis complex (TSC) are at risk for a unique age-related tauopathy. The tauopathy pathogenesis may involve TSC1, TSC2, and related molecular pathways.
ACTA NEUROPATHOLOGICA
(2023)
Article
Cell Biology
Dayan B. Goodenowe, Vijitha Senanayake
Summary: Reduced cognition in the elderly is associated with low levels of plasmalogens, high levels of amyloid plaques and neurofibrillary tangles. Only PL 18:0/22:6, tangles, and flotillin were independently associated with reduced cognition. High brain levels of PL 18:0/22:6 were predictive of normal cognition, while low levels and high levels of tangles or flotillin were predictive of dementia.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Ping-Chieh Pao, Jinsoo Seo, Audrey Lee, Oleg Kritskiy, Debasis Patnaik, Jay Penney, Ravikiran M. Raju, Ute Geigenmuller, M. Catarina Silva, Diane E. Lucente, James F. Gusella, Bradford C. Dickerson, Anjanet Loon, Margaret X. Yu, Michael Bula, Melody Yu, Stephen J. Haggarty, Li-Hue Tsai
Summary: In this study, a 12-amino-acid-long peptide fragment derived from Cdk5 (Cdk5i) was identified. The Cdk5i showed high binding affinity toward the Cdk5/p25 complex and reduced Cdk5/p25 kinase activity, offering therapeutic potential for neurodegenerative diseases associated with Cdk5 hyperactivity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)