scholarly journals Association of Plasma Oligomerized Beta Amyloid with Neurocognitive Battery Using Korean Version of Consortium to Establish a Registry for Alzheimer’s Disease in Health Screening Population

Diagnostics ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 237 ◽  
Author(s):  
Jung-Ju Lee ◽  
Youngki Choi ◽  
Soie Chung ◽  
Dae Hyun Yoon ◽  
Seung Ho Choi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Education ◽  
Brain Mri ◽  
Apoe Genotype ◽  
Amyloid Β ◽  
Health Screening ◽  
Word Recall ◽  
Korean Version ◽  
Word Memory

The increasing prevalence of Alzheimer’s disease (AD) has become a global phenomenon presenting serious social and health challenges. For detecting early molecular changes in the disease, several techniques to measure varied species of amyloid beta in the peripheral blood have been recently developed, but the efforts to associate them with cognitive assessments have yet to produce sufficient data. We prospectively collected participants from the consecutive population who visited our center for brain health screening. In total, 97 participants (F:M = 58:39) aged 69.4 ± 7.52 were assessed. Participants performed the Korean version of the Consortium to Establish a Registry for Alzheimer’s disease (CERAD-K), the clinical dementia rating (CDR), plasma oligomeric amyloid-β (OAβ) level tests, routine blood tests, ApoE genotype, and brain MRI. Among total population, 55.7% had a CDR of 0, and 40.2% had a CDR of 0.5. The results showed that word memory and word recall, and the total scores of the CERAD-K were negatively correlated with the plasma OAβ level. With a cut-off value of 0.78 ng/mL for the OAβ level and a −1.5 standard deviation of age/sex/education adjusted norms for the CERAD-K; naming, word memory, word recall, word recognition, and total score were significantly correlated with the OAβ level. No correlation between the OAβ level and mini-mental status examination was found. Our results demonstrate that the level of plasma OAβ was well correlated with the measure of cognitive function through the CERAD-K in the field data collected from consecutive populations. Studies on longitudinal comparisons with large cohorts will further validate the diagnostic value of plasma OAβ as a useful biomarker for screening AD and predicting progression.

scholarly journals Case of early-onset Alzheimer’s disease with atypical manifestation

2021 ◽  
Vol 34 (1) ◽  
pp. e100283
Author(s):  
Lin Zhu ◽  
Limin Sun ◽  
Lin Sun ◽  
Shifu Xiao
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Manifestation ◽  
Early Onset ◽  
Short Term Memory ◽  
Brain Mri ◽  
Memory Loss ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Fluent Aphasia

Short-term memory decline is the typical clinical manifestation of Alzheimer’s disease (AD). However, early-onset AD usually has atypical symptoms and may get misdiagnosed. In the present case study, we reported a patient who experienced symptoms of memory loss with progressive non-fluent aphasia accompanied by gradual social withdrawal. He did not meet the diagnostic criteria of AD based on the clinical manifestation and brain MRI. However, his cerebrospinal fluid examination showed a decreased level of beta-amyloid 42, and increased total tau and phosphorylated tau. Massive amyloid β-protein deposition by 11C-Pittsburgh positron emission tomography confirmed the diagnosis of frontal variant AD. This case indicated that early-onset AD may have progressive non-fluent aphasia as the core manifestation. The combination of individual and precision diagnosis would be beneficial for similar cases.

Alzheimer’s Disease-Related Neuropathology Among Patients with Medication Treated Type 2 Diabetes in a Community-Based Autopsy Cohort

2021 ◽  
pp. 1-10
Author(s):  
Douglas Barthold ◽  
Laura E. Gibbons ◽  
Zachary A. Marcum ◽  
Shelly L. Gray ◽  
C. Dirk Keene ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Education ◽  
Descriptive Analysis ◽  
Neurofibrillary Tangle ◽  
Apoe Genotype ◽  
Severity Index ◽  
Neuritic Plaque ◽  
Braak Stage ◽  
Total N

Background: Diabetes is a risk factor for Alzheimer’s disease and related dementias (ADRD). Epidemiologic evidence shows an association between diabetes medications and ADRD risk; cell and mouse models show diabetes medication association with AD-related neuropathologic change (ADNC). Objective: This hypothesis-generating analysis aimed to describe autopsy-measured ADNC for individuals who used diabetes medications. Methods: Descriptive analysis of ADNC for Adult Changes in Thought (ACT) Study autopsy cohort who used diabetes medications, including sulfonylureas, insulin, and biguanides; total N = 118. ADNC included amyloid plaque distribution (Thal phasing), neurofibrillary tangle (NFT) distribution (Braak stage), and cortical neuritic plaque density (CERAD score). We also examined quantitative measures of ADNC using the means of standardized Histelide measures of cortical PHF-tau and Aβ 1–42. Adjusted analyses control for age at death, sex, education, APOE genotype, and diabetes complication severity index. Results: Adjusted analyses showed no significant association between any drug class and traditional neuropathologic measures compared to nonusers of that class. In adjusted Histelide analyses, any insulin use was associated with lower mean levels of Aβ 1–42 (–0.57 (CI: –1.12, –0.02)) compared to nonusers. Five years of sulfonylureas and of biguanides use was associated with lower levels of Aβ 1–42 compared to nonusers (–0.15 (CI: –0.28, –0.02), –0.31 (CI: –0.54, –0.07), respectively). Conclusion: Some evidence exists that diabetes medications are associated with lower levels of Aβ 1–42, but not traditional measures of neuropathology. Future studies are needed in larger samples to build understanding of the mechanisms between diabetes, its medications, and ADRD, and to potentially repurpose existing medications for prevention or delay of ADRD.

scholarly journals Association Between Common Variants of APOE, ABCA7, A2M, BACE1, and Cerebrospinal Fluid Biomarkers in Alzheimer’s Disease: Data from the PUMCH Dementia Cohort

2021 ◽  
pp. 1-8
Author(s):  
Liling Dong ◽  
Chenhui Mao ◽  
Caiyan Liu ◽  
Jie Li ◽  
Xinying Huang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Brain Mri ◽  
Apoe Genotype ◽  
Csf Biomarkers ◽  
Common Variants ◽  
College Hospital ◽  
Coding Regions ◽  
The Common

Background: The previous studies have identified several genes in relation to Alzheimer’s disease (AD), such as ABCA7, CR1, etc. A few studies have explored the association between the common variants, mainly in the non-coding regions of these genes, and cerebrospinal fluid (CSF) biomarkers. Fewer studies target the variants in the coding regions. Objective: To illustrate the association between the common variants within or adjacent to the coding regions of AD susceptible genes and CSF biomarkers in AD patients. Methods: 75 sporadic probable AD patients were extracted from the dementia cohort of Peking Union Medical College Hospital. They all had history inquiry, physical examination, blood test, cognitive assessment, brain MRI, CSF testing of Aβ42, 181p-tau, and t-tau, and next-generation DNA sequencing. Sixty-nine common single nucleotide polymorphisms (SNPs) (minor allele frequency > 0.01) within or near the coding region of 13 AD susceptible genes were included in the analysis. Results: The rs7412-CC (APOE) genotype showed lower CSF Aβ42 level and higher p-tau/Aβ42 ratio than the rs7412-CT genotype. The rs3752246-C (ABCA7) allele correlated with lower CSF Aβ42 level. The alternate alleles of six ABCA7 SNPs were related to lower CSF p-tau, including rs3745842, rs3764648, rs3764652, rs4147930, rs4147934 and rs881768. The rs11609582-TT (A2M) genotype showed higher CSF p-tau than the rs11609582-TA genotype. The p-tau/Aβ42 ratio was higher in the rs490460-TT (BACE1) genotype relative to the rs490460-GT genotype. Conclusion: Some common variants within or near the coding regions of APOE, ABCA7, A2M, and BACE1 are associated with CSF Aβ42, p-tau. or p-tau/Aβ42.

scholarly journals Amyloidogenic Nanoplaques in Cerebrospinal Fluid: Relationship to Amyloid Brain Uptake and Clinical Alzheimer’s Disease in a Memory Clinic Cohort

2020 ◽  
Vol 77 (2) ◽  
pp. 831-842 ◽  
Author(s):  
Mari Aksnes ◽  
Ebba Glersen Müller ◽  
Ann Tiiman ◽  
Trine Holt Edwin ◽  
Lars Terenius ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Apoe Genotype ◽  
Amyloid Β ◽  
Correlation Spectroscopy ◽  
Brain Uptake ◽  
Memory Clinic ◽  
Fluorescence Correlation ◽  
Pathological Event

Background: Aggregation of amyloid-β (Aβ) is an early pathological event in Alzheimer’s disease (AD). Consequently, measures of pathogenic aggregated Aβ are attractive biomarkers for AD. Here, we use a recently developed Thioflavin-T-Fluorescence Correlation Spectroscopy (ThT-FCS) assay to quantify structured ThT-responsive protein aggregates, so-called nanoplaques, in the cerebrospinal fluid (CSF). Objective: The overall aim of this work was to assess whether ThT-FCS determined CSF nanoplaque levels could predict amyloid brain uptake as determined by 18F-Flutemetamol PET analysis. Further, we assess whether nanoplaque levels could predict clinical AD. Methods: Nanoplaque levels in the CSF from 54 memory clinic patients were compared between sub-groups classified by 18F-Flutemetamol PET as amyloid-positive or amyloid-negative, and by clinical assessment as AD or non-AD. Results: Nanoplaque levels did not differ between amyloid groups and could not predict brain amyloid uptake. However, nanoplaque levels were significantly increased in patients with clinical AD, and were significant predictors for AD when adjusting for age, sex, cognitive function, and apolipoprotein E (APOE) genotype. Conclusion: The concentration of nanoplaques in the CSF differentiates patients with clinical AD from non-AD patients.

De Novo PS1 Mutation (Pro436Gln) in a Very Early-Onset Posterior Variant of Alzheimer’s Disease Associated with Spasticity: A Case Report

2021 ◽  
pp. 1-6
Author(s):  
Pablo Agüero ◽  
María José Sainz ◽  
Raquel Téllez ◽  
Isabel Lorda ◽  
Almudena Ávila ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
De Novo ◽  
Clinical Phenotype ◽  
Brain Mri ◽  
Amyloid Β ◽  
Strong Impact ◽  
Amyloid Pet ◽  
Posterior Cortex ◽  
Cerebrospinal Fluid Biomarkers

We report a patient with sporadic Alzheimer’s disease with onset in his twenties found to carry the de novo Pro436Gln mutation in the presenilin 1 gene (PS1). Clinical phenotype featured a posterior cortical syndrome with severe visual agnosia and mild limb spasticity with brisk reflexes. Brain MRI and FDG-PET scans revealed severe parieto-occipital atrophy/hypometabolism. Cerebrospinal fluid biomarkers showed a decrease in Aβ 42 level and Aβ 42/40 ratio, increased phospho-tau, and normal total tau. Amyloid PET identified a very high burden of amyloid-β neuritic plaques in the posterior cortex. Similarities between this and two previously reported cases with this variant support that this mutation has a very strong impact on the clinical phenotype and is consistently associated with spasticity.

Cohort-Specific Optimization of Models Predicting Preclinical Alzheimer’s Disease, to Enhance Screening Performance in the Middle of Preclinical Alzheimer’s Disease Clinical Studies

2021 ◽  
pp. 1-10
Author(s):  
K. Sato ◽  
T. Mano ◽  
R. Ihara ◽  
K. Suzuki ◽  
Y. Niimi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Education ◽  
Apoe Genotype ◽  
Standardized Uptake Value ◽  
Asian Population ◽  
Amyloid Pet ◽  
Preclinical Alzheimer’S Disease ◽  
Clinical Dementia Rating ◽  
Preclinical Ad

BACKGROUND: Models that can predict brain amyloid beta (Aβ) status more accurately have been desired to identify participants for clinical trials of preclinical Alzheimer’s disease (AD). However, potential heterogeneity between different cohorts and the limited cohort size have been the reasons preventing the development of reliable models applicable to the Asian population, including Japan. Objectives: We aim to propose a novel approach to predict preclinical AD while overcoming these constraints, by building models specifically optimized for ADNI or for J-ADNI, based on the larger samples from A4 study data. Design & Participants: This is a retrospective study including cognitive normal participants (CDR-global = 0) from A4 study, Alzheimer Disease Neuroimaging Initiative (ADNI), and Japanese-ADNI (J-ADNI) cohorts. Measurements: The model is made up of age, sex, education years, history of AD, Clinical Dementia Rating-Sum of Boxes, Preclinical Alzheimer Cognitive Composite score, and APOE genotype, to predict the degree of amyloid accumulation in amyloid PET as Standardized Uptake Value ratio (SUVr). The model was at first built based on A4 data, and we can choose at which SUVr threshold configuration the A4-based model may achieve the best performance area under the curve (AUC) when applied to the random-split half ADNI or J-ADNI subset. We then evaluated whether the selected model may also achieve better performance in the remaining ADNI or J-ADNI subsets. Result: When compared to the results without optimization, this procedure showed efficacy of AUC improvement of up to approximately 0.10 when applied to the models “without APOE;” the degree of AUC improvement was larger in the ADNI cohort than in the J-ADNI cohort. Conclusions: The obtained AUC had improved mildly when compared to the AUC in case of literature-based predetermined SUVr threshold configuration. This means our procedure allowed us to predict preclinical AD among ADNI or J-ADNI second-half samples with slightly better predictive performance. Our optimizing method may be practically useful in the middle of the ongoing clinical study of preclinical AD, as a screening to further increase the prior probability of preclinical AD before amyloid testing.

scholarly journals Olfactory Impairment is Related to Tau Pathology and Neuroinflammation in Alzheimer’s Disease

2021 ◽  
pp. 1-16
Author(s):  
Julia Klein ◽  
Xinyu Yan ◽  
Aubrey Johnson ◽  
Zeljko Tomljanovic ◽  
James Zou ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Mri ◽  
Amyloid Β ◽  
Cognitive Status ◽  
Odor Identification ◽  
Amyloid Pet ◽  
Tau Pathology ◽  
Olfactory Impairment ◽  
T Tau

Background: Olfactory impairment is evident in Alzheimer’s disease (AD); however, its precise relationships with clinical biomarker measures of tau pathology and neuroinflammation are not well understood. Objective: To determine if odor identification performance measured with the University of Pennsylvania Smell Identification Test (UPSIT) is related to in vivo measures of tau pathology and neuroinflammation. Methods: Cognitively normal and cognitively impaired participants were selected from an established research cohort of adults aged 50 and older who underwent neuropsychological testing, brain MRI, and amyloid PET. Fifty-four participants were administered the UPSIT. Forty-one underwent 18F-MK-6240 PET (measuring tau pathology) and fifty-three underwent 11C-PBR28 PET (measuring TSPO, present in activated microglia). Twenty-three participants had lumbar puncture to measure CSF concentrations of total tau (t-tau), phosphorylated tau (p-tau), and amyloid-β (Aβ 42). Results: Low UPSIT performance was associated with greater18F-MK-6240 binding in medial temporal cortex, hippocampus, middle/inferior temporal gyri, inferior parietal cortex, and posterior cingulate cortex (p <  0.05). Similar relationships were seen for 11C-PBR28. These relationships were primarily driven by amyloid-positive participants. Lower UPSIT performance was associated with greater CSF concentrations of t-tau and p-tau (p <  0.05). Amyloid status and cognitive status exhibited independent effects on UPSIT performance (p <  0.01). Conclusion: Olfactory identification deficits are related to extent of tau pathology and neuroinflammation, particularly in those with amyloid pathophysiology. The independent association of amyloid-positivity and cognitive impairment with odor identification suggests that low UPSIT performance may be a marker for AD pathophysiology in cognitive normal individuals, although impaired odor identification is associated with both AD and non-AD related neurodegeneration. NCT Registration Numbers: NCT03373604; NCT02831283

Inconstant apolipoprotein E (ApoE)-like immunoreactivity in amyloid β protein deposits: relationship with APOE genotype in aging brain and Alzheimer's disease

1996 ◽  
Vol 92 (2) ◽  
pp. 180-185 ◽  
Author(s):  
Toshiki Uchihara ◽  
C. Duyckaerts ◽  
Françoise Lazarini ◽  
Karima Mokhtari ◽  
Danielle Seilhean ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Apoe Genotype ◽  
Amyloid Β ◽  
Aging Brain ◽  
Amyloid Β Protein ◽  
Protein Deposits ◽  
Β Protein

scholarly journals Relationship between Persistent Dizziness and Markers of Alzheimer's disease – Mayo Clinic Study of Aging

2021 ◽  
Author(s):  
RAZAN AL FAKIR
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Education ◽  
Mayo Clinic ◽  
Cognitive Impairments ◽  
Neuropsychiatric Symptoms ◽  
Amyloid Β ◽  
Density Lipoprotein ◽  
Contributing Factors ◽  
Clinic Study

Abstract Persistent dizziness or lightheadedness ranks among the most frequent complaints in primary care. Persistent dizziness is frequently described as a consequence or side effect of defined entities such as cardiovascular, infectious, neurological, and otological disease. Persistent dizziness is potentially disabling and has a distinct impact on participation, psychosocial interaction, and quality of life. We examined the relationship between persistent dizziness or lightheadedness and Alzheimer's disease (AD) markers among 924 individuals aged ≥50 years (52.3% male, mean age 74 years) selected from 5707 individuals who participated in the population-based Mayo Clinic Study of Aging in Olmsted County, Minnesota. Neuropsychiatric symptoms (depression and anxiety), cognitive evaluation (overall and across multiple domains), magnetic resonance imaging for AD-signature "regional thickness," and 11Carbon-Pittsburgh compound B positron emission tomography (11C-PiB PET) for Amyloid deposition are all investigated. Significant contributing factors to persistent dizziness in older adults were found and include [age, sex (male), lower education, high comorbidity index, high-density lipoprotein, balance problems, neuropsychiatric symptoms, cognitive impairments, and AD-signature” regional thickness]. After adjusting for age, sex, education, medical comorbidities, and other variables, a statistically significant association between persistent dizziness/lightheadedness and neuropsychiatric symptoms, and Amyloid-β deposition. This finding implies that the underlying AD biology may drive both the neuropsychiatric symptoms and persistent dizziness or lightheadedness, even before the onset of cognitive impairments and dementia. Further studies are needed to support the findings.

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