scholarly journals Ibrutinib modulates Aβ/tau pathology, neuroinflammation, and cognitive function in mouse models of Alzheimer's disease

Aging Cell ◽  
2021 ◽  
Vol 20 (3) ◽  
Author(s):  
Hyun‐ju Lee ◽  
Seong Gak Jeon ◽  
Jieun Kim ◽  
Ri Jin Kang ◽  
Seong‐Min Kim ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Mouse Models ◽  
Tau Pathology

scholarly journals Regional differences in Alzheimer’s disease pathology confound behavioural rescue after amyloid-β attenuation

Brain ◽  
2019 ◽  
Vol 143 (1) ◽  
pp. 359-373 ◽  
Author(s):  
Christopher D Morrone ◽  
Paolo Bazzigaluppi ◽  
Tina L Beckett ◽  
Mary E Hill ◽  
Margaret M Koletar ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Cognitive Function ◽  
Spatial Memory ◽  
Regional Differences ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Barnes Maze ◽  
Tau Pathology

Abstract Failure of Alzheimer’s disease clinical trials to improve or stabilize cognition has led to the need for a better understanding of the driving forces behind cognitive decline in the presence of active disease processes. To dissect contributions of individual pathologies to cognitive function, we used the TgF344-AD rat model, which recapitulates the salient hallmarks of Alzheimer’s disease pathology observed in patient populations (amyloid, tau inclusions, frank neuronal loss, and cognitive deficits). scyllo-Inositol treatment attenuated amyloid-β peptide in disease-bearing TgF344-AD rats, which rescued pattern separation in the novel object recognition task and executive function in the reversal learning phase of the Barnes maze. Interestingly, neither activities of daily living in the burrowing task nor spatial memory in the Barnes maze were rescued by attenuating amyloid-β peptide. To understand the pathological correlates leading to behavioural rescue, we examined the neuropathology and in vivo electrophysiological signature of the hippocampus. Amyloid-β peptide attenuation reduced hippocampal tau pathology and rescued adult hippocampal neurogenesis and neuronal function, via improvements in cross-frequency coupling between theta and gamma bands. To investigate mechanisms underlying the persistence of spatial memory deficits, we next examined neuropathology in the entorhinal cortex, a region whose input to the hippocampus is required for spatial memory. Reduction of amyloid-β peptide in the entorhinal cortex had no effect on entorhinal tau pathology or entorhinal-hippocampal neuronal network dysfunction, as measured by an impairment in hippocampal response to entorhinal stimulation. Thus, rescue or not of cognitive function is dependent on regional differences of amyloid-β, tau and neuronal network dysfunction, demonstrating the importance of staging disease in patients prior to enrolment in clinical trials. These results further emphasize the need for combination therapeutic approaches across disease progression.

scholarly journals Alzheimer’s-like pathology in aging rhesus macaques: Unique opportunity to study the etiology and treatment of Alzheimer’s disease

2019 ◽  
Vol 116 (52) ◽  
pp. 26230-26238 ◽  
Author(s):  
Amy F. T. Arnsten ◽  
Dibyadeep Datta ◽  
Shannon Leslie ◽  
Sheng-Tao Yang ◽  
Min Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Immunoelectron Microscopy ◽  
Rhesus Monkeys ◽  
Early Stage ◽  
Amyloid Β ◽  
Tau Phosphorylation ◽  
Association Cortex ◽  
Tau Pathology

Although mouse models of Alzheimer’s disease (AD) have provided tremendous breakthroughs, the etiology of later onset AD remains unknown. In particular, tau pathology in the association cortex is poorly replicated in mouse models. Aging rhesus monkeys naturally develop cognitive deficits, amyloid plaques, and the same qualitative pattern and sequence of tau pathology as humans, with tangles in the oldest animals. Thus, aging rhesus monkeys can play a key role in AD research. For example, aging monkeys can help reveal how synapses in the prefrontal association cortex are uniquely regulated compared to the primary sensory cortex in ways that render them vulnerable to calcium dysregulation and tau phosphorylation, resulting in the selective localization of tau pathology observed in AD. The ability to assay early tau phosphorylation states and perform high-quality immunoelectron microscopy in monkeys is a great advantage, as one can capture early-stage degeneration as it naturally occurs in situ. Our immunoelectron microscopy studies show that phosphorylated tau can induce an “endosomal traffic jam” that drives amyloid precursor protein cleavage to amyloid-β in endosomes. As amyloid-β increases tau phosphorylation, this creates a vicious cycle where varied precipitating factors all lead to a similar phenotype. These data may help explain why circuits with aggressive tau pathology (e.g., entorhinal cortex) may degenerate prior to producing significant amyloid pathology. Aging monkeys therefore can play an important role in identifying and testing potential therapeutics to protect the association cortex, including preventive therapies that are challenging to test in humans.

Transgenic mouse models for Alzheimer's disease: the role of GSK-3β in combined amyloid and tau-pathology

2006 ◽  
Vol 162 (10) ◽  
pp. 903-907 ◽  
Author(s):  
D. Muyllaert ◽  
D. Terwel ◽  
P. Borghgraef ◽  
H. Devijver ◽  
I. Dewachter ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mouse ◽  
Mouse Models ◽  
Transgenic Mouse Models ◽  
Tau Pathology ◽  
Gsk 3Β

O2-12-04: STALLED BLOOD FLOW IN BRAIN CAPILLARIES IS RESPONSIBLE FOR REDUCED CORTICAL PERFUSION AND IMPACTS COGNITIVE FUNCTION IN MOUSE MODELS OF ALZHEIMER'S DISEASE

2006 ◽  
Vol 14 (7S_Part_12) ◽  
pp. P651-P652
Author(s):  
Oliver Bracko ◽  
Jean C. Cruz Hernandez ◽  
Brendah N. Njiru ◽  
Madison Swallow ◽  
Jieyu Zheng ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Flow ◽  
Cognitive Function ◽  
Mouse Models ◽  
Brain Capillaries ◽  
Cortical Perfusion

The effects of caloric restriction and its mimetics in Alzheimer's disease through autophagy pathways

2020 ◽  
Vol 11 (2) ◽  
pp. 1211-1224 ◽  
Author(s):  
Yi Yang ◽  
Lihui Zhang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Neurodegenerative Disease ◽  
Caloric Restriction ◽  
Rodent Models ◽  
Older Individuals ◽  
Amyloid Burden ◽  
Tau Pathology

AD is a neurodegenerative disease that commonly occurs among older individuals. Caloric restriction and its mimetics have been shown to alleviate amyloid burden, tau pathology, and improve cognitive function of rodent models of AD by activating autophagy.

scholarly journals Amyloid Reduction by Amyloid-  Vaccination Also Reduces Mouse Tau Pathology and Protects from Neuron Loss in Two Mouse Models of Alzheimer's Disease

2009 ◽  
Vol 29 (25) ◽  
pp. 7957-7965 ◽  
Author(s):  
D. M. Wilcock ◽  
N. Gharkholonarehe ◽  
W. E. Van Nostrand ◽  
J. Davis ◽  
M. P. Vitek ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Tau Pathology ◽  
Neuron Loss

scholarly journals Postsynaptic degeneration as revealed by PSD-95 reduction occurs after advanced Aβ and tau pathology in transgenic mouse models of Alzheimer’s disease

2011 ◽  
Vol 122 (3) ◽  
pp. 285-292 ◽  
Author(s):  
Charles Y. Shao ◽  
Suzanne S. Mirra ◽  
Hameetha B. R. Sait ◽  
Todd C. Sacktor ◽  
Einar M. Sigurdsson
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mouse ◽  
Mouse Models ◽  
Transgenic Mouse Models ◽  
Tau Pathology
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