scholarly journals Reduced synchrony in alpha oscillations during life predicts post mortem neurofibrillary tangle density in early‐onset and atypical Alzheimer's disease

2021 ◽  
Author(s):  
Kamalini G. Ranasinghe ◽  
Cathrine Petersen ◽  
Kiwamu Kudo ◽  
Danielle Mizuiri ◽  
Katherine P. Rankin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Onset ◽  
Neurofibrillary Tangle ◽  
Post Mortem ◽  
Alpha Oscillations ◽  
Atypical Alzheimer’S Disease

scholarly journals Distribution of pathological hallmarks and association with post‐mortem MRI cortical thickness in typical and atypical Alzheimer’s disease

2020 ◽  
Vol 16 (S1) ◽  
Author(s):  
Laura E. Jonkman ◽  
Baayla D.C. Boon ◽  
Irene Frigerio ◽  
Martijn D. Steenwijk ◽  
Paolo Preziosa ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cortical Thickness ◽  
Post Mortem ◽  
Atypical Alzheimer’S Disease

scholarly journals Post-mortem T2*- weighted MRI imaging of cortical iron reflects severity of Alzheimer’s Disease

2018 ◽  
Author(s):  
Marjolein Bulk ◽  
Boyd Kenkhuis ◽  
Linda M. van der Graaf ◽  
Jelle J. Goeman ◽  
Remco Natté ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Distribution Pattern ◽  
Early Onset ◽  
Late Onset ◽  
Ex Vivo ◽  
Post Mortem ◽  
Mri Contrast ◽  
Mri Changes ◽  
Cortical Distribution

AbstractThe value of iron-based MRI changes for the diagnosis and staging of Alzheimer’s disease (AD) depends on an association between cortical iron accumulation and AD pathology. Therefore, this study determined the cortical distribution pattern of MRI contrast changes in cortical regions selected based on the known distribution pattern of tau pathology and investigated whether MRI contrast changes reflect the underlying AD pathology in the different lobes.-weighted MRI was performed on post-mortem cortical tissue of controls, late-onset AD, and early-onset AD followed by histology and correlation analyses. Combining ex-vivo high-resolution MRI and histopathology revealed that: LOAD and EOAD have a different distribution pattern of AD pathological hallmarks and MRI contrast changes over the cortex, with EOAD showing more severe MRI changes; (2) per lobe, severity of AD pathological hallmarks correlates with iron accumulation, and hence with MRI. Therefore, iron-sensitive MRI sequences allow detection of the cortical distribution pattern of AD pathology ex-vivo.AbbreviationsADAlzheimer’s diseaseEOADearly-onset ADGMgray matterIRPiron regulating proteinsLOADlate-onset ADMCImild cognitive impairmentPBSphosphate buffered salineQSMquantitative susceptibility mappingWMwhite matter

scholarly journals A novel missense variant in ACAA1 contributes to early-onset Alzheimer’s disease, impairs lysosomal function, and facilitates amyloid-β pathology and cognitive decline

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Rongcan Luo ◽  
Yu Fan ◽  
Jing Yang ◽  
Maosen Ye ◽  
Deng-Feng Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Onset ◽  
Neurofibrillary Tangle ◽  
Amyloid Β ◽  
Neuronal Loss ◽  
Missense Variant ◽  
Lysosomal Function

AbstractAlzheimer’s disease (AD) is characterized by progressive synaptic dysfunction, neuronal death, and brain atrophy, with amyloid-β (Aβ) plaque deposits and hyperphosphorylated tau neurofibrillary tangle accumulation in the brain tissue, which all lead to loss of cognitive function. Pathogenic mutations in the well-known AD causal genes including APP, PSEN1, and PSEN2 impair a variety of pathways, including protein processing, axonal transport, and metabolic homeostasis. Here we identified a missense variant rs117916664 (c.896T>C, p.Asn299Ser [p.N299S]) of the acetyl-CoA acyltransferase 1 (ACAA1) gene in a Han Chinese AD family by whole-genome sequencing and validated its association with early-onset familial AD in an independent cohort. Further in vitro and in vivo evidence showed that ACAA1 p.N299S contributes to AD by disturbing its enzymatic activity, impairing lysosomal function, and aggravating the Aβ pathology and neuronal loss, which finally caused cognitive impairment in a murine model. Our findings reveal a fundamental role of peroxisome-mediated lysosomal dysfunction in AD pathogenesis.

P1-359: NEUROPATHOLOGICAL FINDINGS OF AN EARLY-ONSET DEMENTIA CASE WITH ATYPICAL ALZHEIMER'S DISEASE: HOW CHALLENGING CAN THE CLINICAL DIAGNOSIS OF MIXED AD BE?

2006 ◽  
Vol 14 (7S_Part_8) ◽  
pp. P432-P432
Author(s):  
Roberta Diehl Rodriguez ◽  
Mariana Molina ◽  
Renata P. Leite ◽  
Rafaela Sabadin ◽  
Leonel Tadao Takada ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Diagnosis ◽  
Early Onset ◽  
Early Onset Dementia ◽  
Dementia Case ◽  
Atypical Alzheimer’S Disease

Distinct social-behavioral changes in frontotemporal dementia and early onset Alzheimer's disease

2014 ◽  
Author(s):  
Joseph P. Barsuglia ◽  
Michelle J. Mather ◽  
Hemali V. Panchal ◽  
Aditi Joshi ◽  
Elvira Jimenez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Frontotemporal Dementia ◽  
Early Onset ◽  
Behavioral Changes ◽  
Early Onset Alzheimer’S Disease

Depressive Symptoms and APOE ε2 Broad the Natural History in Presenilin-1 E280A Familial Early-Onset Alzheimer's Disease

2018 ◽  
Author(s):  
Natalia Acosta-Baena ◽  
Carlos Mario Lopera-Gómez ◽  
Mario César Jaramillo-Elorza ◽  
Margarita Giraldo-Chica ◽  
Mauricio Arcos-Burgos ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Depressive Symptoms ◽  
Natural History ◽  
Early Onset ◽  
Presenilin 1 ◽  
Early Onset Alzheimer’S Disease

Exploring the Role of Aggregated Proteomes in the Pathogenesis of Alzheimer’s Disease

2020 ◽  
Vol 21 (12) ◽  
pp. 1164-1173
Author(s):  
Siju Ellickal Narayanan ◽  
Nikhila Sekhar ◽  
Rajalakshmi Ganesan Rajamma ◽  
Akash Marathakam ◽  
Abdullah Al Mamun ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Precursor Protein ◽  
Early Onset ◽  
Late Onset ◽  
Precursor Protein ◽  
Brain Disorder ◽  
Amyloid Aβ ◽  
T Tau

: Alzheimer’s disease (AD) is a progressive brain disorder and one of the most common causes of dementia and death. AD can be of two types; early-onset and late-onset, where late-onset AD occurs sporadically while early-onset AD results from a mutation in any of the three genes that include amyloid precursor protein (APP), presenilin 1 (PSEN 1) and presenilin 2 (PSEN 2). Biologically, AD is defined by the presence of the distinct neuropathological profile that consists of the extracellular β-amyloid (Aβ) deposition in the form of diffuse neuritic plaques, intraneuronal neurofibrillary tangles (NFTs) and neuropil threads; in dystrophic neuritis, consisting of aggregated hyperphosphorylated tau protein. Elevated levels of (Aβ), total tau (t-tau) and phosphorylated tau (ptau) in cerebrospinal fluid (CSF) have become an important biomarker for the identification of this neurodegenerative disease. The aggregation of Aβ peptide derived from amyloid precursor protein initiates a series of events that involve inflammation, tau hyperphosphorylation and its deposition, in addition to synaptic dysfunction and neurodegeneration, ultimately resulting in dementia. The current review focuses on the role of proteomes in the pathogenesis of AD.

Identification of a Pathogenic PSEN1 Ala285Val Mutation Associated with Early-Onset Alzheimer’s Disease

2020 ◽  
Vol 17 (5) ◽  
pp. 438-445
Author(s):  
Van Giau Vo ◽  
Jung-Min Pyun ◽  
Eva Bagyinszky ◽  
Seong S.A. An ◽  
Sang Y. Kim
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Temporal Lobe ◽  
Early Onset ◽  
Parietal Lobe ◽  
Disease Diagnosis ◽  
Random Coil ◽  
Magnetic Resonance Imaging Scan ◽  
Preclinical Ad ◽  
Early Onset Alzheimer’S Disease

Background: Presenilin 1 (PSEN1) was suggested as the most common causative gene of early onset Alzheimer’s Disease (AD). Methods: Patient who presented progressive memory decline in her 40s was enrolled in this study. A broad battery of neuropsychological tests and neuroimaging was applied to make the diagnosis. Genetic tests were performed in the patient to evaluate possible mutations using whole exome sequencing. The pathogenic nature of missense mutation and its 3D protein structure prediction were performed by in silico prediction programs. Results: A pathogenic mutation in PSEN1 (NM_000021.3: c.1027T>C p.Ala285Val), which was found in a Korean EOAD patient. Magnetic resonance imaging scan showed mild left temporal lobe atrophy. Hypometabolism appeared through 18F-fludeoxyglucose Positron Emission Tomography (FDG-PET) scanning in bilateral temporal and parietal lobe, and 18F-Florbetaben-PET (FBB-PET) showed increased amyloid deposition in bilateral frontal, parietal, temporal lobe and hence presumed preclinical AD. Protein modeling showed that the p.Ala285Val is located in the random coil region and could result in extra stress in this region, resulting in the replacement of an alanine residue with a valine. This prediction was confirmed previous in vitro studies that the p.Trp165Cys resulted in an elevated Aβ42/Aβ40 ratio in both COS-1 and HEK293 cell lines compared that of wild-type control. Conclusion: Together, the clinical characteristics and the effect of the mutation would facilitate our understanding of PSEN1 in AD pathogenesis for the disease diagnosis and treatment. Future in vivo study is needed to evaluate the role of PSEN1 p.Ala285Val mutation in AD progression.

Genetic analysis of vietnamese patients with early-onset alzheimer's disease

2021 ◽  
pp. 1-10
Author(s):  
Trang Mai Tong ◽  
Thuy Thi Hong Dao ◽  
Loc Phuoc Doan ◽  
Dat Thanh Nguyen ◽  
Quynh-Tho Thi Nguyen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Analysis ◽  
Early Onset ◽  
Early Onset Alzheimer’S Disease
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