scholarly journals Patients with Alzheimer's disease have increased cellular amyloid uptake

2022 ◽  
Author(s):  
Dmitry V Zaretsky ◽  
Maria V Zaretskaia ◽  
Yaroslav I Molkov
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Onset ◽  
Late Onset ◽  
Strong Negative Correlation ◽  
Cognitively Normal ◽  
Intracellular Degradation ◽  
Estimated Parameters ◽  
Amyloid Aβ ◽  
Using Data

Amyloid plaques are the main signature of Alzheimer's disease (AD). Beta-amyloid (Aβ) concentration in cerebrospinal fluid (CSF-Aβ) and the density of amyloid depositions have a strong negative correlation. However, AD patients have lower CSF-Aβ levels compared to cognitively normal people even after accounting for this correlation. The goal of this study was to infer variations of parameters in Aβ metabolism of AD patients that underlie this difference using data from the Alzheimer's Disease Neuroimaging Initiative cohort. We found that AD patients had dramatically increased rates of cellular amyloid uptake compared to individuals with normal cognition (NC). A group with late-onset mild cognitive impairment (LMCI) also exhibited stronger amyloid uptake, however this was less pronounced than in the AD group. Estimated parameters in the early-onset MCI group did not differ significantly from those in the NC group. Aβ cytotoxicity depends on both the amount of peptide internalized by cells and its intracellular degradation into toxic products. Based on our results, we speculate that AD and LMCI are associated with increased cellular amyloid uptake which leads to faster disease progression, whereas the early-onset MCI may be mediated by the increased production of toxic amyloid metabolites.

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.

scholarly journals Hippocampo-Horn Percentage and Parietal Atrophy Score for Easy Visual Assessment of Brain Atrophy on Magnetic Resonance Imaging in Early- and Late-Onset Alzheimer’s Disease

2021 ◽  
pp. 1-8
Author(s):  
David Silhan ◽  
Olga Pashkovska ◽  
Ales Bartos ◽  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hip Hop ◽  
Brain Atrophy ◽  
Early Onset ◽  
Late Onset ◽  
Brain Mri ◽  
Resonance Imaging ◽  
Cognitively Normal

Background: Magnetic resonance imaging (MRI) visual scales of brain atrophy are important for differential diagnosis of dementias in routine clinical practice. Atrophy patterns in early- and late-onset Alzheimer’s disease (AD) can be different according to some studies. Objective: Our goal was to assess brain atrophy patterns in early- and late-onset AD using our recently developed simple MRI visual scales and evaluate their reliability. Methods: We used Hippocampo-horn percentage (Hip-hop) and Parietal Atrophy Score (PAS) to compare mediotemporal and parietal atrophy on brain MRI among 4 groups: 26 patients with early-onset AD, 21 younger cognitively normal persons, 32 patients with late-onset AD, 36 older cognitively normal persons. Two raters scored all brain MRI to assess reliability of the Hip-hop and PAS. Brain MRI were obtained from Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Results: The patients with early-onset AD had significantly more pronounced mediotemporal and also parietal atrophy bilaterally compared to the controls (both p <  0.01). The patients with late-onset AD had significantly more pronounced only mediotemporal atrophy bilaterally compared to the controls (p <  0.000001), but parietal lobes were the same. Intra-rater and inter-rater reliability of both visual scales Hip-hop and PAS were almost perfect in all cases (weighted-kappa value ranged from 0.90 to 0.99). Conclusion: While mediotemporal atrophy detected using Hip-hop is universal across whole AD age spectrum, parietal atrophy detected using PAS is worth rating only in early-onset AD. Hip-hop and PAS are very reliable MRI visual scales.

scholarly journals The clinical utility of gene testing for Alzheimer’s disease

2011 ◽  
Vol 3 (1) ◽  
pp. 1 ◽  
Author(s):  
Emily R. Atkins ◽  
Peter K. Panegyres
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Onset ◽  
Late Onset ◽  
Association Studies ◽  
Susceptibility Gene ◽  
Genome Wide Association Studies ◽  
Apoe Ε4 ◽  
Gene Testing ◽  
A Genome

Alzheimer’s disease (AD) is the largest cause of dementia, affecting 35.6 million people in 2010. Amyloid precursor protein, presenilin 1 and presenilin 2 mutations are known to cause familial early-onset AD, whereas apolipoprotein E (APOE) ε4 is a susceptibility gene for late-onset AD. The genes for phosphatidylinositol- binding clathrin assembly protein, clusterin and complement receptor 1 have recently been described by genome-wide association studies as potential risk factors for lateonset AD. Also, a genome association study using single neucleotide polymorphisms has identified an association of neuronal sortilin related receptor and late-onset AD. Gene testing, and also predictive gene testing, may be of benefit in suspected familial early-onset AD however it adds little to the diagnosis of lateonset AD and does not alter the treatment. We do not recommend APOE ε4 genotyping.

scholarly journals The Correlations Between Plasma Fibrinogen With Amyloid-Beta and Tau Levels in Patients With Alzheimer’s Disease

2021 ◽  
Vol 14 ◽  
Author(s):  
Dong-Yu Fan ◽  
Hao-Lun Sun ◽  
Pu-Yang Sun ◽  
Jie-Ming Jian ◽  
Wei-Wei Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Plasma Fibrinogen ◽  
Cognitively Normal ◽  
Amyloid Aβ ◽  
And Gender ◽  
T Tau ◽  
The Relationship ◽  
Phosphorylated Tau 181 ◽  
Normal Controls

Recent studies show that fibrinogen plays a role in the pathogenesis of Alzheimer’s disease (AD), which may be crucial to neurovascular damage and cognitive impairment. However, there are few clinical studies on the relationship between fibrinogen and AD. 59 11C-PiB-PET diagnosed AD patients and 76 age- and gender-matched cognitively normal controls were included to analyze the correlation between plasma β-amyloid (Aβ) and tau levels with fibrinogen levels. 35 AD patients and 76 controls with cerebrospinal fluid (CSF) samples were included to further analyze the correlation between CSF Aβ and tau levels with fibrinogen levels. In AD patients, plasma fibrinogen levels were positively correlated with plasma Aβ40 and Aβ42 levels, and negatively correlated with CSF Aβ42 levels. Besides, fibrinogen levels were positively correlated with CSF total tau (t-tau), and phosphorylated tau-181 (p-tau) levels and positively correlated with the indicators of Aβ deposition in the brain, such as t-tau/Aβ42, p-tau/Aβ42 levels. In normal people, fibrinogen levels lack correlation with Aβ and tau levels in plasma and CSF. This study suggests that plasma fibrinogen levels are positively correlated with Aβ levels in the plasma and brain in AD patients. Fibrinogen may be involved in the pathogenesis of AD.

scholarly journals HERPESVIRUS INFECTIONS AND CLINICAL-IMMUNOLOGIC INTERACTIONS IN PATIENTS WITH EARLY-ONSET ALZHEIMER’S DISEASE AND LATE-ONSET ALZHEIMER’S DISEASE

2021 ◽  
Vol 23 (4) ◽  
pp. 805-812
Author(s):  
I. K. Malashenkova ◽  
D. P. Ogurtsov ◽  
S. A. Krynskiy ◽  
N. A. Khailov ◽  
N. D. Selezneva ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Viral Load ◽  
Early Onset ◽  
Late Onset ◽  
Adaptive Immune Response ◽  
Subsequent Development ◽  
Chronic Infections ◽  
Immune Parameters ◽  
Inflammatory Protein

Alzheimer’s disease (AD) is currently the most common cause of dementia. A significant role in the pathogenesis of AD belongs to the activation of the mechanisms of neuroinflammation. There is a hypothesis that chronic infections may play a role in the maintenance of the inflammatory response in AD. The aim of this work was to study the detection rate and DNA level of herpesviruses, as well as their possible relationship with the level of the key cytokines and with clinical parameters of AD in patients with early and late onset. 30 patients with AD and 33 healthy volunteers were enrolled. The quantitative determination of DNA of CMV, EBV, HHV-6, HHV-7 was carried out by PCR. The level of cytokines and soluble IL-1β antagonist (IL-1ra) in the blood was determined by ELISA. Herpesvirus infection with increased viral load was determined if at least one of the criteria was present: 1) DNA level of EBV and/or HHV-6 > 10,000 copies/ml in saliva; 2) presence of DNA of at least one of the EBV, HHV-6, HHV-7 viruses in the blood. In the subgroup of patients with early onset and increased viral load, there was a higher increase in the levels of a number of cytokines: proinflammatory IL-8 and IL-12, a Th2-cytokine IL-4, a cytokine of the adaptive immune response IL-2. However, the level of the anti-inflammatory protein IL-1ra was lower than in the controls. These changes may indicate a dysregulation of the antiviral response, with a predominance of activation of systemic inflammation and Th2-mediated reactions. Also, in early onset AD the increased viral load was associated with lower scores on Boston naming test. The results indicate that in studies of AD mechanisms and in the search for prognostic markers of the disease, it is important to take into account the heterogeneity of AD in terms of genetic predisposition factors, risk factors, immune parameters and clinical data. Such approach is necessary for the subsequent development of personalized approaches to the prevention and treatment of AD. 

scholarly journals Prevalence and Severity of Neuropsychiatric Symptoms in Early- Versus Late-Onset Alzheimer’s Disease

2019 ◽  
Vol 34 (7-8) ◽  
pp. 433-438 ◽  
Author(s):  
Sarah Baillon ◽  
Amy Gasper ◽  
Frances Wilson-Morkeh ◽  
Megan Pritchard ◽  
Amala Jesu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Onset ◽  
Late Onset ◽  
Functional Dependence ◽  
Neuropsychiatric Symptoms ◽  
Caregiver Distress ◽  
Duration Of Illness ◽  
Symptom Prevalence ◽  
Early Onset Alzheimer’S Disease

Background: The study aimed to compare neuropsychiatric symptoms (NPS) in people with early-onset Alzheimer’s disease (EOAD) and late-onset AD (LOAD). Methods: Fifty-six participants with LOAD and 24 participants with EOAD having mild dementia were assessed for NPS for their frequency, severity, and caregiver distress as measured by Neuropsychiatry Inventory (NPI) along with assessments of cognition and functional dependence. Results: Participants with EOAD and LOAD were not significantly different for total NPI score ( P = .057). Early-onset Alzheimer disease had greater prevalence of all the NPS except apathy. Participants with EOAD were significantly worse on anxiety ( P = .03), irritability ( P = .01), and sleep ( P < .01) subscales and their carers significantly more distressed by their irritability ( P = .002) and sleeping patterns ( P = .005). Regression analysis showed that higher NPI score was associated with longer duration of illness in EOAD and higher functional dependence in LOAD. Conclusions: The NPS severity was similar between EOAD and LOAD although EOAD had higher symptom prevalence and carer distress.

Assoziationen zwischen Cholesterin, APOB und früher Alzheimer-Erkrankung

2020 ◽  
Vol 88 (01) ◽  
pp. 4
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Onset ◽  
Late Onset ◽  
Alzheimer Krankheit ◽  
Early Onset Alzheimer’S Disease

Hohe Cholesterinwerte sind ein Risikofaktor für die Entwicklung der altersbedingten, späten Form der Alzheimer-Krankheit, der „Late-onset Alzheimer`s disease“ (LOAD). Doch wie die seltenere, frühe Form, die „Early-onset Alzheimer‘s disease“ (EOAD) mit Cholesterin zusammenhängt, war bisher unklar. In dieser Studie untersuchten die Forscher Assoziationen zwischen Cholesterinwerten und EOAD, sowie zugrunde liegende genetische Mechanismen.

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