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Alzheimer, amyloid beta, apolipoprotein

Ling Li, Fan Zeng, Yu-Hui Liu, Hui-Yun Li, Shu-Yang Dong, Ze-Yan Peng, Yan-Jiang Wang, Hua-Dong Zhou
Polymorphisms of the cholesterol-24S-hydroxylase (CYP46A1) and apolipoprotein E (APOE) genes are risk factors for Alzheimer's disease (AD). Plasma level of 24S-hydroxcholesterol (24-OHC), the metabolite of cholesterol, is thought to correlate with AD. The present study investigated the correlation between these genetic factors and blood 24-OHC and amyloid-beta (Aβ) levels in AD patients. Association analysis, logistic regression, and linear regression were used to analyze the correlation of CYP46A1 and APOE genotypes with blood 24-OHC and Aβ levels and AD risk...
March 7, 2018: Molecular Neurobiology
Marci M Horn, Kristen M Kennedy, Karen M Rodrigue
Decline in associative memory abilities is a common cognitive complaint among older adults and is detectable in both normal aging and in prodromal Alzheimer's disease (AD). Subjective memory (SM) complaints may serve as an earlier marker of these mnemonic changes; however, previous research examining the predictive utility of SM to observed memory performance yielded inconsistent results. This inconsistency is likely due to other sources of variance that occur with memory decline such as mood/depression issues, presence of apolipoprotein E (APOE ε4) genotype, or beta-amyloid deposition...
February 2018: Psychology and Aging
Elizabeth S Chan, Christopher Chen, Tuck Wah Soong, Boon-Seng Wong
Apolipoprotein E4 (ApoE4) is the strongest genetic risk factor for sporadic Alzheimer's disease (AD), where inheritance of this isoform predisposes development of AD in a gene dose-dependent manner. Although the mode of action of ApoE4 on AD onset and progression remains unknown, we have previously shown that ApoE4, and not ApoE3 expression, resulted in insulin signaling deficits in the presence of amyloid beta (Aβ). However, these reports were not conducted with clinical samples that more accurately reflect human disease...
February 15, 2018: Neuromolecular Medicine
Nancy J Donovan, Joseph J Locascio, Gad A Marshall, Jennifer Gatchel, Bernard J Hanseeuw, Dorene M Rentz, Keith A Johnson, Reisa A Sperling
OBJECTIVE: To understand the role of depressive symptoms in preclinical Alzheimer's disease, it is essential to define their temporal relationship to Alzheimer's proteinopathies in cognitively normal older adults. The study objective was to examine associations of brain amyloid beta and longitudinal measures of depression and depressive symptom clusters in a cognitively normal sample of older adults. METHOD: A total of 270 community-dwelling, cognitively normal elderly individuals underwent baseline Pittsburgh compound B (PiB) positron emission tomography (PET) measures of cortical aggregate amyloid beta and annual assessments with the 30-item Geriatric Depression Scale (GDS)...
January 12, 2018: American Journal of Psychiatry
C Báez-Becerra, F Filipello, A Sandoval-Hernández, H Arboleda, G Arboleda
Alzheimer's disease (AD) is a devastating neurodegenerative disease characterized by beta-amyloid (Aβ) accumulation and neurofibrillary tangles formation in the brain which are associated to synaptic deficits and dementia. Liver X receptor (LXR) agonists have been demonstrated to revert of pathologic and cognitive defects in murine models of AD through the regulation of Apolipoprotein E, ATP-Binding Cassette A1 (ABCA1), by dampening neuroinflammation and also by reducing the levels of amyloid-β (Aβ) accumulation in the brain...
January 3, 2018: Neurotoxicity Research
Sepideh Shokouhi, William R Riddle, Hakmook Kang
Introduction: Previously, we discussed several critical barriers in including [18F] fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) imaging of preclinical Alzheimer's disease (AD) subjects. These factors included the reference region selection and intensity normalization of PET images and the within- and across-subject variability of affected brain regions. In this study, we utilized a novel FDG-PET analysis, the regional FDG time correlation coefficient, rFTC, that can address and resolve these barriers and provide a more sensitive way of monitoring longitudinal changes in metabolism of cognitively normal elderly adults...
2017: Clinical Interventions in Aging
Miranka Wirth, Alexandre Bejanin, Renaud La Joie, Eider M Arenaza-Urquijo, Julie Gonneaud, Brigitte Landeau, Audrey Perrotin, Florence Mézenge, Vincent de La Sayette, Béatrice Desgranges, Gaël Chételat
Alzheimer's disease (AD) is characterized by the presence of β-amyloid (Aβ) deposition and neurodegeneration. To seek for signs of such pathologies, we compared regional biomarker degrees and patterns of Aβ deposition, glucose hypometabolism, and gray matter volume (GMV) reduction in 3 groups at risk of AD. In elderly carriers of the apolipoprotein E ε4 (APOE4, n = 17), patients with subjective cognitive decline (n = 16), and patients with mild cognitive impairment (n = 30), head-to-head intermodality comparisons were performed on cross-sectional structural magnetic resonance images as well as 18F-fluorodeoxyglucose and 18F-florbetapir positron emission tomography scans...
March 2018: Neurobiology of Aging
Jeffrey N Savas, Yi-Zhi Wang, Laura A DeNardo, Salvador Martinez-Bartolome, Daniel B McClatchy, Timothy J Hark, Natalie F Shanks, Kira A Cozzolino, Mathieu Lavallée-Adam, Samuel N Smukowski, Sung Kyu Park, Jeffery W Kelly, Edward H Koo, Terunaga Nakagawa, Eliezer Masliah, Anirvan Ghosh, John R Yates
Amyloid beta (Aβ) peptides impair multiple cellular pathways and play a causative role in Alzheimer's disease (AD) pathology, but how the brain proteome is remodeled by this process is unknown. To identify protein networks associated with AD-like pathology, we performed global quantitative proteomic analysis in three mouse models at young and old ages. Our analysis revealed a robust increase in Apolipoprotein E (ApoE) levels in nearly all brain regions with increased Aβ levels. Taken together with prior findings on ApoE driving Aβ accumulation, this analysis points to a pathological dysregulation of the ApoE-Aβ axis...
November 28, 2017: Cell Reports
C Lopez Lopez, A Caputo, F Liu, M E Riviere, M-L Rouzade-Dominguez, R G Thomas, J B Langbaum, R Lenz, E M Reiman, A Graf, P N Tariot
Alzheimer's disease pathology begins decades before the onset of clinical symptoms. This provides an opportunity for interventional clinical trials to potentially delay or prevent the onset of cognitive impairment or dementia. CNP520 (a beta-site-amyloid precursor protein-cleaving enzyme inhibitor) is in clinical development for the treatment of preclinical Alzheimer's disease under the Alzheimer's Prevention Initiative Generation Program. The Alzheimer's Prevention Initiative is a public-private partnership intended to accelerate the evaluation of Alzheimer's disease prevention therapies...
2017: Journal of Prevention of Alzheimer's Disease
Jung-Lung Hsu, Wei-Ju Lee, Yi-Chu Liao, Shuu-Jiun Wang, Jong-Ling Fuh
BACKGROUND: Clusterin and beta-amyloid (Aβ) are involved in the pathogenesis of Alzheimer's disease (AD). The clinical significance of plasma clusterin and Aβ in AD progression remains controversial. METHODS: We recruited 322 patients with AD and 88 controls between August 2012 and June 2013. All participants were evaluated at baseline with a clinical assessment, Mini-Mental State Examination (MMSE), and Clinical Dementia Rating (CDR) scales. Patients with AD were evaluated annually with the MMSE and Neuropsychiatric Inventory (NPI) scale during the 2-year follow-up period...
November 23, 2017: Alzheimer's Research & Therapy
Deepshikha Bhardwaj, Connie Mitra, Chandrakala Aluganti Narasimhulu, Aladdin Riad, Mitsushita Doomra, Sampath Parthasarathy
Alzheimer's disease (AD) is an age-related neurodegenerative disorder of the brain. The presence of amyloid-beta (Aβ) plaques, neurofibrillary tangles (NFTs), loss of neurons, synapses, and altered sensory perceptions, including memory loss, delineate AD. However, the cause of AD is not clearly known. Several genetic and nongenetic factors have been implicated in the disease. Of the genes, the ɛ4 allele of apolipoprotein E is the largest known genetic risk factor of AD. This review article focuses on the various genetic and other predisposing factors that account for AD, pathophysiology of the disease, and the mechanisms by which Aβ plaques and NFTs are formed and could affect AD brain...
December 2017: Journal of Medicinal Food
Lars Michels, Muthuraman Muthuraman, Abdul R Anwar, Spyros Kollias, Sandra E Leh, Florian Riese, Paul G Unschuld, Michael Siniatchkin, Anton F Gietl, Christoph Hock
The assessment of effects associated with cognitive impairment using electroencephalography (EEG) power mapping allows the visualization of frequency-band specific local changes in oscillatory activity. In contrast, measures of coherence and dynamic source synchronization allow for the study of functional and effective connectivity, respectively. Yet, these measures have rarely been assessed in parallel in the context of mild cognitive impairment (MCI) and furthermore it has not been examined if they are related to risk factors of Alzheimer's disease (AD) such as amyloid deposition and apolipoprotein ε4 (ApoE) allele occurrence...
2017: Frontiers in Aging Neuroscience
Jerome Robert, Emily B Button, Brian Yuen, Megan Gilmour, Kevin Kang, Arvin Bahrabadi, Sophie Stukas, Wenchen Zhao, Iva Kulic, Cheryl L Wellington
Amyloid plaques, consisting of deposited beta-amyloid (Aβ), are a neuropathological hallmark of Alzheimer's Disease (AD). Cerebral vessels play a major role in AD, as Aβ is cleared from the brain by pathways involving the cerebrovasculature, most AD patients have cerebrovascular amyloid (cerebral amyloid angiopathy (CAA), and cardiovascular risk factors increase dementia risk. Here we present a notable advance in vascular tissue engineering by generating the first functional 3-dimensioinal model of CAA in bioengineered human vessels...
October 10, 2017: ELife
Amane Tateno, Takeshi Sakayori, Woo Chan Kim, Michihiko Koeda, Shinichiro Kumita, Hidenori Suzuki, Yoshiro Okubo
INTRODUCTION: The plasma concentration of beta-amyloid (Aβ) has been considered another biomarker of Alzheimer's disease and was reportedly associated with cortical Aβ accumulation. METHODS: We analyzed 28 subjects with apolipoprotein E4 (ApoE4; E4 group) and 89 subjects without ApoE4 (non-E4 group) to determine the association between cortical Aβ accumulation by standard uptake value ratio with [(18)F]florbetapir positron emission tomography and plasma Aβ1-40 and Aβ1-42...
2017: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Sofía Fernández-de Retana, Alex Montañola, Paula Marazuela, Maialen De La Cuesta, Aina Batlle, Marc Fatar, Saskia Grudzenski, Joan Montaner, Mar Hernández-Guillamon
Beyond the crucial role of apolipoprotein A-I (ApoA-I) on peripheral cholesterol metabolism, this apolipoprotein has also been implicated in beta amyloid (Aβ)-related neuropathologies. ApoA-I-Milano (M) is a mutated variant, which showed increased vasoprotective properties compared to ApoA-I-wild type in models of atherosclerosis and cardiovascular damage. We speculated that ApoA-I-M may also protect Aβ-affected vasculature and reverse some of the pathological features associated with Alzheimer's disease (AD)...
December 2017: Neurobiology of Aging
Farshad Falahati, Daniel Ferreira, J-Sebastian Muehlboeck, Maria Eriksdotter, Andrew Simmons, Lars-Olof Wahlund, Eric Westman
BACKGROUND: A disease severity index (SI) for Alzheimer's disease (AD) has been proposed that summarizes MRI-derived structural measures into a single score using multivariate data analysis. OBJECTIVES: To longitudinally evaluate the use of the SI to monitor disease progression and predict future progression to AD in mild cognitive impairment (MCI). Further, to investigate the association between longitudinal change in the SI and cognitive impairment, Apolipoprotein E (APOE) genotype as well as the levels of cerebrospinal fluid amyloid-beta 1-42 (Aβ) peptide...
2017: NeuroImage: Clinical
Hyo Jung Choi, Min Soo Byun, Dahyun Yi, Bo Kyung Sohn, Jun Ho Lee, Jun-Young Lee, Yu Kyung Kim, Dong Young Lee
BACKGROUND: The present study investigated the relationships between thyroid hormone serum levels or thyroid-stimulating hormone (TSH) and two Alzheimer's disease (AD)-specific biomarkers, cerebral amyloid beta (Aβ) burden and glucose metabolism, in AD-signature brain regions in cognitively normal (CN) middle-aged and older individuals. METHODS: This study assessed 148 CN individuals who received comprehensive clinical and neuropsychological assessments that included (11)C-Pittsburgh Compound B (PiB)-positron emission tomography (PET) scans, (18)F-deoxyglucose (FDG)-PET scans, and the quantification of serum triiodothyronine (T3), free T3, free thyroxine (fT4), and TSH levels...
August 17, 2017: Alzheimer's Research & Therapy
Daniel A Llano, Saurabh Bundela, Raksha A Mudar, Viswanath Devanarayan
To determine if a multi-analyte cerebrospinal fluid (CSF) peptide signature can be used to differentiate Alzheimer's Disease (AD) and normal aged controls (NL), and to determine if this signature can also predict progression from mild cognitive impairment (MCI) to AD, analysis of CSF samples was done on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. The profiles of 320 peptides from baseline CSF samples of 287 subjects over a 3-6 year period were analyzed. As expected, the peptide most able to differentiate between AD vs...
2017: PloS One
Hoau-Yan Wang, Caryn Trocmé-Thibierge, Andres Stucky, Sanket M Shah, Jessica Kvasic, Amber Khan, Philippe Morain, Isabelle Guignot, Eva Bouguen, Karine Deschet, Maria Pueyo, Elisabeth Mocaer, Pierre-Jean Ousset, Bruno Vellas, Vera Kiyasova
BACKGROUND: The apolipoprotein E ε4 (APOE4) genotype is a prominent late-onset Alzheimer's disease (AD) risk factor. ApoE4 disrupts memory function in rodents and may contribute to both plaque and tangle formation. METHODS: Coimmunoprecipitation and Western blot detection were used to determine: 1) the effects of select fragments from the apoE low-density lipoprotein (LDL) binding domain and recombinant apoE subtypes on amyloid beta (Aβ)42-α7 nicotinic acetylcholine receptor (α7nAChR) interaction and tau phosphorylation in rodent brain synaptosomes; and 2) the level of Aβ42-α7nAChR complexes in matched controls and patients with mild cognitive impairment (MCI) and dementia due to AD with known APOE genotypes...
July 27, 2017: Alzheimer's Research & Therapy
Ana Gb Rabelo, Camila Vl Teixeira, Thamires Nc Magalhães, Ana Flávia Mk Carletti-Cassani, Augusto Cs Amato Filho, Helena Pg Joaquim, Leda L Talib, Orestes Forlenza, Patrícia Ao Ribeiro, Rodrigo Secolin, Iscia Lopes-Cendes, Fernando Cendes, Marcio Lf Balthazar
Introduction The search for a reliable neuroimaging biomarker in Alzheimer's disease is a matter of intense research. The presence of cerebral microbleeds seems to be a potential biomarker. However, it is not clear if the presence of microbleeds has clinical usefulness to differentiate mild Alzheimer's disease and amnestic mild cognitive impairment from normal aging. We aimed to verify if microbleed prevalence differs among three groups: mild Alzheimer's disease, amnestic mild cognitive impairment due to Alzheimer's disease, and normal controls...
October 2017: Neuroradiology Journal
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