scholarly journals Human Brain and Blood N-Glycome Profiling in Alzheimer’s Disease and Alzheimer’s Disease-Related Dementias

2021 ◽  
Vol 13 ◽  
Author(s):  
Lei Yu ◽  
Zhiguang Huo ◽  
Jingyun Yang ◽  
Helena Palma-Gudiel ◽  
Patricia A. Boyle ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Postmortem Brain ◽  
Post Translational Modification ◽  
Baseline Serum ◽  
Postmortem Brain Tissue ◽  
Dorsolateral Prefrontal ◽  
Protein Functions ◽  
Health And Disease

Glycosylation, the process of adding glycans (i.e., sugars) to proteins, is the most abundant post-translational modification. N-glycosylation is the most common form of glycosylation, and the N-glycan moieties play key roles in regulating protein functions and many other biological processes. Thus, identification and quantification of N-glycome (complete repertoire of all N-glycans in a sample) may provide new sources of biomarkers and shed light on health and disease. To date, little is known about the role of altered N-glycome in Alzheimer’s Disease and Alzheimer’s Disease-related Dementias (AD/ADRD). The current study included 45 older adults who had no cognitive impairment (NCI) at baseline, followed and examined annually, and underwent brain autopsy after death. During about 12-year follow-up, 15 developed mild cognitive impairment (MCI), 15 developed AD, and 15 remained NCI. Relative abundances of N-glycans in serum at 2 time points (baseline and proximate to death, ∼12.3 years apart) and postmortem brain tissue (dorsolateral prefrontal cortex) were quantified using MALDI-TOF-MS. Regression models were used to test the associations of N-glycans with AD/ADRD phenotypes. We detected 71 serum and 141 brain N-glycans, of which 46 were in common. Most serum N-glycans had mean fold changes less than one between baseline and proximate to death. The cross-tissue N-glycan correlations were weak. Baseline serum N-glycans were more strongly associated with AD/ADRD compared to change in serum N-glycans over time and brain N-glycans. The N-glycan associations were observed in both AD and non-AD neuropathologies. To our knowledge, this is the first comprehensive glycomic analysis in both blood and brain in relation to AD pathology. Our results suggest that altered N-glycans may serve as mechanistic biomarkers for early diagnosis and progression of AD/ADRD.

scholarly journals Financial Capacity and Regional Cerebral Tau in Cognitively Normal Older Adults, Mild Cognitive Impairment, and Alzheimer’s Disease Dementia

2020 ◽  
pp. 1-10
Author(s):  
Christopher Gonzalez ◽  
Nicole S. Tommasi ◽  
Danielle Briggs ◽  
Michael J. Properzi ◽  
Rebecca E. Amariglio ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Early Stage ◽  
Cognitively Normal ◽  
Financial Capacity ◽  
Posterior Cingulate ◽  
Dorsolateral Prefrontal

Background: Financial capacity is often one of the first instrumental activities of daily living to be affected in cognitively normal (CN) older adults who later progress to amnestic mild cognitive impairment (MCI) and Alzheimer’s disease (AD) dementia. Objective: The objective of this study was to investigate the association between financial capacity and regional cerebral tau. Methods: Cross-sectional financial capacity was assessed using the Financial Capacity Instrument –Short Form (FCI-SF) in 410 CN, 199 MCI, and 61 AD dementia participants who underwent flortaucipir tau positron emission tomography from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Linear regression models with backward elimination were used with FCI-SF total score as the dependent variable and regional tau and tau-amyloid interaction as predictors of interest in separate analyses. Education, age sex, Rey Auditory Verbal Learning Test Total Learning, and Trail Making Test B were used as covariates. Results: Significant associations were found between FCI-SF and tau regions (entorhinal: p <  0.001; inferior temporal: p <  0.001; dorsolateral prefrontal: p = 0.01; posterior cingulate: p = 0.03; precuneus: p <  0.001; and supramarginal gyrus: p = 0.005) across all participants. For the tau-amyloid interaction, significant associations were found in four regions (amyloid and dorsolateral prefrontal tau interaction: p = 0.005; amyloid and posterior cingulate tau interaction: p = 0.005; amyloid and precuneus tau interaction: p <  0.001; and amyloid and supramarginal tau interaction: p = 0.002). Conclusion: Greater regional tau burden was modestly associated with financial capacity impairment in early-stage AD. Extending this work with longitudinal analyses will further illustrate the utility of such assessments in detecting clinically meaningful decline, which may aid clinical trials of early-stage AD.

scholarly journals The APOE ε4/ε4 Genotype Potentiates Vascular Fibrin(Ogen) Deposition in Amyloid-Laden Vessels in the Brains of Alzheimer's Disease Patients

2013 ◽  
Vol 33 (8) ◽  
pp. 1251-1258 ◽  
Author(s):  
Karin Hultman ◽  
Sidney Strickland ◽  
Erin H Norris
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Critical Role ◽  
Apoe Genotype ◽  
Postmortem Brain ◽  
Amyloid Angiopathy ◽  
Apoe Ε4 ◽  
Cerebrovascular Dysfunction ◽  
Postmortem Brain Tissue ◽  
Clotting Protein

Evidence indicates a critical role for cerebrovascular dysfunction in Alzheimer's disease (AD) pathophysiology. We have shown that fibrin(ogen), the principal blood-clotting protein, is deposited in the AD neurovasculature and interacts with beta-amyloid (Ab), resulting in increased formation of blood clots. As apolipoprotein E (ApoE), a lipid-transporting protein with three human isoforms (E2, E3, and E4), also binds to Aβ, we hypothesized that ApoE and fibrin(ogen) may have a combined effect on the vascular pathophysiology in AD. We assessed whether APOE genotype differentially influences vascular fibrin(ogen) deposition in postmortem brain tissue using immunohistochemistry. An increased deposition of fibrin(ogen) was observed in AD cases compared with non-demented controls, and there was a strong correlation between cerebral amyloid angiopathy (CAA) severity and fibrin(ogen) deposition. Moreover, brains from AD cases homozygous for APOE ε4 showed increased deposition of fibrin(ogen), specifically in CAA- and oligomeric Aβ-positive vessels compared with AD APOE ε2 and ε3 allele carriers, an effect that was not directly linked to CAA severity and cerebrovascular atherosclerosis. These data further support a role for fibrin(ogen) in AD pathophysiology and link the APOE ε4/ε4 genotype with increased thrombosis and/or impaired fibrinolysis in the human AD brain.

scholarly journals proNGF Measurement in Cerebrospinal Fluid Samples of a Large Cohort of Living Patients With Alzheimer's Disease by a New Automated Immunoassay

2021 ◽  
Vol 13 ◽  
Author(s):  
Francesca Malerba ◽  
Ivan Arisi ◽  
Rita Florio ◽  
Chiara Zecca ◽  
Maria Teresa Dell'Abate ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Molecular Size ◽  
Fold Increase ◽  
Postmortem Brain ◽  
Subjective Memory ◽  
Postmortem Brain Tissue ◽  
Significant Difference ◽  
New Biomarkers

The discovery of new biomarkers for Alzheimer's disease (AD) is essential for an accurate diagnosis, to conceive new strategies of treatments, and for monitoring the efficacy of potential disease-modifying therapies in clinical trials. proNGF levels in the cerebrospinal fluid (CSF) represent a promising diagnostic biomarker for AD, but its validation was hampered by the absence of a reliable immunoassay. In the literature, proNGF is currently measured in postmortem brain tissue by semiquantitative immunoblot. Here we describe the development and validation of a new method to measure proNGF in the CSF of living patients. This method, based on molecular size separation by capillary electrophoresis, is automated and shows a 40-fold increase in sensitivity with respect to the proNGF immunoblot, largely used in literature, and is robust, specific, and scalable to high-throughput. We have measured proNGF in the cerebrospinal fluid of 84 living patients with AD, 13 controls, and 15 subjective memory complaints (SMC) subjects. By comparing the proNGF levels in the three groups, we found a very significant difference between proNGF levels in AD samples compared with both controls and SMC subjects, while no significant difference was found between SMC and controls. Because of the development of this new immunoassay, we are ready to explore the potentiality of proNGF as a new biomarker for AD or subgroups thereof, as well as for other neurodegenerative diseases.

scholarly journals Failure To Detect Chlamydia pneumoniaein the Late-Onset Alzheimer's Brain

2000 ◽  
Vol 38 (7) ◽  
pp. 2591-2594 ◽  
Author(s):  
Robert H. Ring ◽  
Joseph M. Lyons
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Chlamydia Pneumoniae ◽  
Late Onset ◽  
Brain Regions ◽  
Postmortem Brain ◽  
Respiratory Pathogen ◽  
Specific Gene ◽  
Tissue Samples ◽  
Postmortem Brain Tissue

Epidemiological studies have yet to identify a single cause for the most common late-onset form of Alzheimer's disease. The common respiratory pathogen Chlamydia pneumoniae recently has been implicated as a risk factor for this form of Alzheimer's disease. Were this true, there would be a dramatic shift in current paradigms of Alzheimer's disease research and treatment. In the absence of published confirmation, we obtained postmortem brain tissue from late-onset Alzheimer's disease patients (n = 15) and representative controls (n = 5) and extracted DNA from up to six separate brain regions in each instance, including those areas particularly relevant to Alzheimer's disease neuropathology. Each sample of DNA (n = 101) was assayed five times or more for the presence of C. pneumoniae DNA using a nested-PCR protocol targeting a species-specific gene sequence coding for the major outer membrane protein of this organism. We were unable unequivocally to detect C. pneumoniae in any of the 101 samples tested by PCR and failed to culture the organism from tissue samples. We conclude that C. pneumoniae is neither strongly nor uniquely associated with the neuropathology seen in late-onset Alzheimer's disease.

P3-126: USING RNA-SEQ TO IDENTIFY RNA EDITING IN CONTROL AND ALZHEIMER'S DISEASE POSTMORTEM BRAIN TISSUE

2006 ◽  
Vol 14 (7S_Part_21) ◽  
pp. P1115-P1116
Author(s):  
Sharvari Vadeyar ◽  
Francesca North ◽  
James Turton ◽  
Tamar Guetta-Baranes ◽  
Sally Chappell ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Tissue ◽  
Rna Editing ◽  
Postmortem Brain ◽  
Rna Seq ◽  
Postmortem Brain Tissue

scholarly journals Correlation of proton transverse relaxation rates (R2) with iron concentrations in postmortem brain tissue from alzheimer's disease patients

2006 ◽  
Vol 57 (1) ◽  
pp. 172-180 ◽  
Author(s):  
Michael J. House ◽  
Timothy G. St. Pierre ◽  
Kris V. Kowdley ◽  
Thomas Montine ◽  
James Connor ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Tissue ◽  
Postmortem Brain ◽  
Relaxation Rates ◽  
Transverse Relaxation ◽  
Postmortem Brain Tissue ◽  
Iron Concentrations

scholarly journals TMS–EEG Co-Registration in Patients with Mild Cognitive Impairment, Alzheimer’s Disease and Other Dementias: A Systematic Review

2021 ◽  
Vol 11 (3) ◽  
pp. 303
Author(s):  
Raffaele Nardone ◽  
Luca Sebastianelli ◽  
Viviana Versace ◽  
Davide Ferrazzoli ◽  
Leopold Saltuari ◽  
...  
Keyword(s):  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Brain Connectivity ◽  
Central Area ◽  
Inverse Correlation ◽  
Combined Use ◽  
Cortical Responses ◽  
Dorsolateral Prefrontal

An established method to assess effective brain connectivity is the combined use of transcranial magnetic stimulation with simultaneous electroencephalography (TMS–EEG) because TMS-induced cortical responses propagate to distant anatomically connected brain areas. Alzheimer’s disease (AD) and other dementias are associated with changes in brain networks and connectivity, but the underlying pathophysiology of these processes is poorly defined. We performed here a systematic review of the studies employing TMS–EEG co-registration in patients with dementias. TMS–EEG studies targeting the motor cortex have revealed a significantly reduced TMS-evoked P30 in AD patients in the temporo-parietal cortex ipsilateral to stimulation side as well as in the contralateral fronto-central area, and we have demonstrated a deep rearrangement of the sensorimotor system even in mild AD patients. TMS–EEG studies targeting other cortical areas showed alterations of effective dorsolateral prefrontal cortex connectivity as well as an inverse correlation between prefrontal-to-parietal connectivity and cognitive impairment. Moreover, TMS–EEG analysis showed a selective increase in precuneus neural activity. TMS–EEG co-registrations can also been used to investigate whether different drugs may affect cognitive functions in patients with dementias.

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