An 80-year-old man with dementia demonstrated cerebellar hemorrhage. Autopsy revealed pathology compatible with Alzheimer's disease and cerebral amyloid angiopathy (CAA). CAA was more prevalent in the occipital lobe than in the frontal, parietal, and temporal lobes; however, amyloid-β (Aβ)-containing senile plaques were less abundant in the occipital cortex than in the other cortices. In the cerebellum, abundant CAA-involved vessels were observed in the subarachnoid space and molecular layer and to a lesser extent in the Purkinje and granule layers. On consecutive sections, Aβ immunohistochemistry revealed senile plaques and CAA-involved vessels with strong immunoreactivity whereas Aβ immunohistochemistry identfied CAA-involved vessels with strong immunoreactivity and senile plaques with weak immunoreactivity in the cerebellar cortices.
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http://dx.doi.org/10.1111/neup.12758 | DOI Listing |
J Prev Alzheimers Dis
January 2025
School of Health and Biomedical Sciences, RMIT University, 220 3-5 Plenty Road, Bundoora VIC 3082, Australia. Electronic address:
Alzheimer's Disease (AD) is a chronic neurodegenerative disorder characterized by the accumulation of toxic amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs) of tau protein in the brain. Microglia, key immune cells of the central nervous system, play an important role in AD development and progression, primarily through their responses to Aβ and NFTs. Initially, microglia can clear Aβ, but in AD, chronic activation overwhelms protective mechanisms, leading to sustained neuroinflammation that enhances plaque toxicity, setting off a damaging cycle that affects neurons, astrocytes, cerebral vasculature, and other microglia.
View Article and Find Full Text PDFJ Prev Alzheimers Dis
January 2025
CenExel iResearch, Atlanta, GA, USA.
Background: Soluble species of multimeric amyloid-beta including globular amyloid-beta oligomers (AβOs) and linear amyloid-beta protofibrils are toxic to neurons. Sabirnetug (ACU193) is a humanized monoclonal antibody, raised against globular species of soluble AβO, that has over 650-fold greater binding affinity for AβOs over monomers and appears to have relatively little binding to amyloid plaque.
Objectives: To assess safety, pharmacokinetics, and exploratory measures including target engagement, biomarker effects, and clinical efficacy of sabirnetug in participants with early symptomatic Alzheimer's disease (AD; defined as mild cognitive impairment and mild dementia due to AD).
J Neuroimmune Pharmacol
January 2025
Pharmacy Department, Baotou Central Hospital, Baotou, 014040, Inner Mongolia, China.
Microglial polarization and ferroptosis are important pathological features in Alzheimer's disease (AD). Ghrelin, a brain-gut hormone, has potential neuroprotective effects in AD. This study aimed to explore the potential mechanisms by which ghrelin regulates the progression of AD, as well as the crosstalk between microglial polarization and ferroptosis.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Biochemistry, Faculty of Medicine, Level 17 Preclinical Building, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia.
Alzheimer's disease (AD) poses a significant worldwide health challenge, requiring novel approaches for improved models and treatment development. This comprehensive review emphasises the systematic development and improvement of a biomimetic brain environment to address the shortcomings of existing AD models and enhance the efficiency of screening potential drug treatments. We identify drawbacks in traditional models and emphasise the necessity for more physiologically accurate systems through an in-depth analysis of current literature.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Physicochemical Drug Analysis, Jagiellonian University Medical College, Medyczna Str. 9, 30-688 Kraków, Poland.
Alzheimer's disease, the most common form of dementia, is characterized by the deposition of amyloid plaques and neurofibrillary tangles in the brain, leading to the loss of neurons and a decline in a person's memory and cognitive function. As a multifactorial disease, Alzheimer's involves multiple pathogenic mechanisms, making its treatment particularly challenging. Current drugs approved for the treatment of Alzheimer's disease only alleviate symptoms but cannot stop the progression.
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