scholarly journals Diet, nutrients and metabolism: cogs in the wheel driving Alzheimer's disease pathology?

2015 ◽  
Vol 113 (10) ◽  
pp. 1499-1517 ◽  
Author(s):  
Rhona Creegan ◽  
Wendy Hunt ◽  
Alexandra McManus ◽  
Stephanie R. Rainey-Smith
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Symptoms ◽  
Aged Care ◽  
Ageing Population ◽  
People With Dementia ◽  
Stage Disease ◽  
Custodial Care ◽  
Global Statistics ◽  
End Stage

Alzheimer's disease (AD), the most common form of dementia, is a chronic, progressive neurodegenerative disease that manifests clinically as a slow global decline in cognitive function, including deterioration of memory, reasoning, abstraction, language and emotional stability, culminating in a patient with end-stage disease, totally dependent on custodial care. With a global ageing population, it is predicted that there will be a marked increase in the number of people diagnosed with AD in the coming decades, making this a significant challenge to socio-economic policy and aged care. Global estimates put a direct cost for treating and caring for people with dementia at $US604 billion, an estimate that is expected to increase markedly. According to recent global statistics, there are 35·6 million dementia sufferers, the number of which is predicted to double every 20 years, unless strategies are implemented to reduce this burden. Currently, there is no cure for AD; while current therapies may temporarily ameliorate symptoms, death usually occurs approximately 8 years after diagnosis. A greater understanding of AD pathophysiology is paramount, and attention is now being directed to the discovery of biomarkers that may not only facilitate pre-symptomatic diagnosis, but also provide an insight into aberrant biochemical pathways that may reveal potential therapeutic targets, including nutritional ones. AD pathogenesis develops over many years before clinical symptoms appear, providing the opportunity to develop therapy that could slow or stop disease progression well before any clinical manifestation develops.

The Involvement of Post-Translational Modifications in Alzheimer's Disease

2018 ◽  
Vol 15 (4) ◽  
pp. 313-335 ◽  
Author(s):  
Serena Marcelli ◽  
Massimo Corbo ◽  
Filomena Iannuzzi ◽  
Lucia Negri ◽  
Fabio Blandini ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Modification ◽  
Neurodegenerative Disorder ◽  
Amyloid Β ◽  
Normal Function ◽  
Ageing Population ◽  
Covalent Bonds ◽  
Post Translational Modifications ◽  
Related Proteins

Background: Alzheimer's disease (AD) is a neurodegenerative disorder recognized as the most common cause of chronic dementia among the ageing population. AD is histopathologically characterized by progressive loss of neurons and deposits of insoluble proteins, primarily composed of amyloid-β pelaques and neurofibrillary tangles (NFTs). Methods: Several molecular processes contribute to the formation of AD cellular hallmarks. Among them, post-translational modifications (PTMs) represent an attractive mechanism underlying the formation of covalent bonds between chemical groups/peptides to target proteins, which ultimately result modified in their function. Most of the proteins related to AD undergo PTMs. Several recent studies show that AD-related proteins like APP, Aβ, tau, BACE1 undergo post-translational modifications. The effect of PTMs contributes to the normal function of cells, although aberrant protein modification, which may depend on many factors, can drive the onset or support the development of AD. Results: Here we will discuss the effect of several PTMs on the functionality of AD-related proteins potentially contributing to the development of AD pathology. Conclusion: We will consider the role of Ubiquitination, Phosphorylation, SUMOylation, Acetylation and Nitrosylation on specific AD-related proteins and, more interestingly, the possible interactions that may occur between such different PTMs.

scholarly journals Mitochondrial complex I abnormalities is associated with tau and clinical symptoms in mild Alzheimer’s disease

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Tatsuhiro Terada ◽  
Joseph Therriault ◽  
Min Su Peter Kang ◽  
Melissa Savard ◽  
Tharick Ali Pascoal ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Dysfunction ◽  
Complex I ◽  
Clinical Symptoms ◽  
Mitochondrial Complex I ◽  
Braak Stage ◽  
Mitochondrial Complex ◽  
Temporal Area

Abstract Background Mitochondrial electron transport chain abnormalities have been reported in postmortem pathological specimens of Alzheimer’s disease (AD). However, it remains unclear how amyloid and tau are associated with mitochondrial dysfunction in vivo. The purpose of this study is to assess the local relationships between mitochondrial dysfunction and AD pathophysiology in mild AD using the novel mitochondrial complex I PET imaging agent [18F]BCPP-EF. Methods Thirty-two amyloid and tau positive mild stage AD dementia patients (mean age ± SD: 71.1 ± 8.3 years) underwent a series of PET measurements with [18F]BCPP-EF mitochondrial function, [11C]PBB3 for tau deposition, and [11C] PiB for amyloid deposition. Age-matched normal control subjects were also recruited. Inter and intrasubject comparisons of levels of mitochondrial complex I activity, amyloid and tau deposition were performed. Results The [18F]BCPP-EF uptake was significantly lower in the medial temporal area, highlighting the importance of the mitochondrial involvement in AD pathology. [11C]PBB3 uptake was greater in the temporo-parietal regions in AD. Region of interest analysis in the Braak stage I-II region showed significant negative correlation between [18F]BCPP-EF SUVR and [11C]PBB3 BPND (R = 0.2679, p = 0.04), but not [11C] PiB SUVR. Conclusions Our results indicated that mitochondrial complex I is closely associated with tau load evaluated by [11C]PBB3, which might suffer in the presence of its off-target binding. The absence of association between mitochondrial complex I dysfunction with amyloid load suggests that mitochondrial dysfunction in the trans-entorhinal and entorhinal region is a reflection of neuronal injury occurring in the brain of mild AD.

scholarly journals Induced Pluripotent Stem Cell-Derived Neural Precursors Improve Memory, Synaptic and Pathological Abnormalities in a Mouse Model of Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1802
Author(s):  
Enrique Armijo ◽  
George Edwards ◽  
Andrea Flores ◽  
Jorge Vera ◽  
Mohammad Shahnawaz ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Symptoms ◽  
Memory Loss ◽  
Amyloid Β ◽  
Cerebral Atrophy ◽  
Brain Inflammation ◽  
Neural Precursors ◽  
Model Of Alzheimer’S Disease ◽  
Induced Pluripotent

Alzheimer’s disease (AD) is the most common type of dementia in the elderly population. The disease is characterized by progressive memory loss, cerebral atrophy, extensive neuronal loss, synaptic alterations, brain inflammation, extracellular accumulation of amyloid-β (Aβ) plaques, and intracellular accumulation of hyper-phosphorylated tau (p-tau) protein. Many recent clinical trials have failed to show therapeutic benefit, likely because at the time in which patients exhibit clinical symptoms the brain is irreversibly damaged. In recent years, induced pluripotent stem cells (iPSCs) have been suggested as a promising cell therapy to recover brain functionality in neurodegenerative diseases such as AD. To evaluate the potential benefits of iPSCs on AD progression, we stereotaxically injected mouse iPSC-derived neural precursors (iPSC-NPCs) into the hippocampus of aged triple transgenic (3xTg-AD) mice harboring extensive pathological abnormalities typical of AD. Interestingly, iPSC-NPCs transplanted mice showed improved memory, synaptic plasticity, and reduced AD brain pathology, including a reduction of amyloid and tangles deposits. Our findings suggest that iPSC-NPCs might be a useful therapy that could produce benefit at the advanced clinical and pathological stages of AD.

scholarly journals The Role of Salivary Biomarkers in the Early Diagnosis of Alzheimer’s Disease and Parkinson’s Disease

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 371
Author(s):  
Patrycja Pawlik ◽  
Katarzyna Błochowiak
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Early Diagnosis ◽  
Neurodegenerative Diseases ◽  
Diagnostic Tool ◽  
Clinical Symptoms ◽  
Early Screening ◽  
Salivary Biomarkers

Many neurodegenerative diseases present with progressive neuronal degeneration, which can lead to cognitive and motor impairment. Early screening and diagnosis of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are necessary to begin treatment before the onset of clinical symptoms and slow down the progression of the disease. Biomarkers have shown great potential as a diagnostic tool in the early diagnosis of many diseases, including AD and PD. However, screening for these biomarkers usually includes invasive, complex and expensive methods such as cerebrospinal fluid (CSF) sampling through a lumbar puncture. Researchers are continuously seeking to find a simpler and more reliable diagnostic tool that would be less invasive than CSF sampling. Saliva has been studied as a potential biological fluid that could be used in the diagnosis and early screening of neurodegenerative diseases. This review aims to provide an insight into the current literature concerning salivary biomarkers used in the diagnosis of AD and PD. The most commonly studied salivary biomarkers in AD are β-amyloid1-42/1-40 and TAU protein, as well as α-synuclein and protein deglycase (DJ-1) in PD. Studies continue to be conducted on this subject and researchers are attempting to find correlations between specific biomarkers and early clinical symptoms, which could be key in creating new treatments for patients before the onset of symptoms.

Delayed help seeking behavior in dementia care: preliminary findings from the Clinical Pathway for Alzheimer's Disease in China (CPAD) study

2015 ◽  
Vol 28 (2) ◽  
pp. 211-219 ◽  
Author(s):  
Mei Zhao ◽  
Xiaozhen Lv ◽  
Maimaitirexiati Tuerxun ◽  
Jincai He ◽  
Benyan Luo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Family History ◽  
Clinical Pathway ◽  
Help Seeking ◽  
Univariate Analysis ◽  
Positive Family History ◽  
Dementia Care ◽  
Factors Associated ◽  
People With Dementia

ABSTRACTBackground:The prevalence and factors associated with delays in help seeking for people with dementia in China are unknown.Methods:Within 1,010 consecutively registered participants in the Clinical Pathway for Alzheimer's Disease in China (CPAD) study (NCT01779310), 576 persons with dementia (PWDs) and their informants reported the estimated time from symptom onset to first medical visit seeking diagnosis. Univariate analysis of general linear model was used to examine the potential factors associated with the delayed diagnosis seeking.Results:The median duration from the first noticeable symptom to the first visit seeking diagnosis or treatment was 1.77 years. Individuals with a positive family history of dementia had longer duration (p= 0.05). Compared with other types of dementia, people with vascular dementia (VaD) were referred for diagnosis earliest, and the sequence for such delays was: VaD < Alzheimer's disease (AD) < frontotemporal dementia (FTD) (p< 0.001). Subtypes of dementia (p< 0.001), family history (p= 0.01), and education level (p= 0.03) were associated with the increased delay in help seeking.Conclusions:In China, seeking diagnosis for PWDs is delayed for approximately 2 years, even in well-established memory clinics. Clinical features, family history, and less education may impede help seeking in dementia care.

scholarly journals “End-Stage” Neurofibrillary Tangle Pathology in Preclinical Alzheimer's Disease: Fact or Fiction?

2011 ◽  
Vol 25 (3) ◽  
pp. 445-453 ◽  
Author(s):  
Erin L. Abner ◽  
Richard J. Kryscio ◽  
Frederick A. Schmitt ◽  
Karen S. SantaCruz ◽  
Gregory A. Jicha ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurofibrillary Tangle ◽  
Preclinical Alzheimer’S Disease ◽  
Tangle Pathology ◽  
End Stage

Longitudinal study of medication use in caregivers of people with Alzheimer’s disease – Kuopio ALSOVA study

Dementia ◽  
2018 ◽  
Vol 19 (5) ◽  
pp. 1573-1585
Author(s):  
Tarja Välimäki ◽  
Julia FM Gilmartin-Thomas ◽  
J Simon Bell ◽  
Tuomas Selander ◽  
Anne M Koivisto
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Family Caregivers ◽  
Social Insurance ◽  
Medication Use ◽  
Self Report ◽  
Rank Test ◽  
Kappa Statistics ◽  
Prescription Register ◽  
People With Dementia

Background The longitudinal pattern of medication use among family caregivers of people with dementia is not well understood, despite the potential for medication over- or under-use. Objectives To investigate caregiver medication use over a five-year follow-up using data obtained via self-report and from a national prescription register, and compare agreement between medication data obtained from the two sources. Methods Medication data for 222 family caregivers of people with Alzheimer’s disease were obtained via self-report and from the Finnish Social Insurance Institution. Generalised estimating equations, Kappa statistics and related samples Wilcoxon signed rank test were used to analyse medication use over time. Results The mean number of medications used by caregivers increased from 3.4 to 4.1 (self-reported current regular medications) and 2.4 to 2.8 (reimbursed prescription medications during the past 90 days) over five years (p < 0.001). Significantly, more medications were identified via self-report (mean 3.6, SD = 3.3) than the national prescription register (mean 2.6, SD = 2.4, Z= –12.300, p < 0.001). Agreement between the two data sources was good for cardiovascular medications and anti-hypertensives (Kappa = 0.883–0.967, p < 0.001) and medications for acid-related disorders (Kappa = 0.508–0.092, p < 0.001). Agreement was moderate for analgesics (Kappa = 0.281–0.477, p < 0.001) and psychotropics (Kappa = 0.281–0.562, p < 0.002). The proportion of caregivers using five or more medications increased from 27.5% to 44.6% (self-report), and 16.7% to 27.7% (register) (p < 0.001). Conclusion Caregivers use an increasing number of medications in the first five years of caring for persons with dementia, and self-report using a higher number of medications than data from the national prescription register suggest.

scholarly journals Cross-cultural adaptation of the German version of the Quality of Life in Alzheimer's Disease scale - Nursing Home version (QoL-AD NH)

2016 ◽  
Vol 28 (8) ◽  
pp. 1399-1400 ◽  
Author(s):  
Martin Nikolaus Dichter ◽  
Eva-Maria Wolschon ◽  
Gabriele Meyer ◽  
Sascha Köpke
Keyword(s):  
Quality Of Life ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Community Dwelling ◽  
Positive Effects ◽  
People With Dementia ◽  
The Us ◽  
Dementia Research ◽  
Almost All

Dementia is a chronic and currently incurable syndrome. Therefore, quality of life (QoL) is a major goal when caring for people with dementia (Gibson et al., 2010) and a major outcome in dementia research (Moniz-Cook et al., 2008). The measurement of QoL, especially proxy-rating, is challenging because of the proxy-perspective (Pickard and Knight, 2005), reliability (Dichter et al., 2016), validity (O'Rourke et al., 2015), and responsiveness (Perales et al., 2013). Probably due to these challenges, it has not been possible to show positive effects for QoL in almost all non-pharmacological interventions for people with dementia (Cooper et al., 2012). One recommended (Moniz-Cook et al., 2008) and frequently used instrument is the Quality of Life in Alzheimer's Disease scale (QoL-AD), which was originally developed in the US for community-dwelling people with dementia. The QoL-AD consists of 13 items based on a 4-point Likert scale ranging from “1”=poor to “4”=excellent (Logsdon et al., 1999). The original instrument has been adapted for people living in nursing homes (NH) by Edelmann et al. (2005).

Is Olfactory Epithelium Biopsy Useful for Confirming Alzheimer’s Disease?

2018 ◽  
Vol 128 (3) ◽  
pp. 184-192 ◽  
Author(s):  
Maria Dantas Costa Lima Godoy ◽  
Marco Aurélio Fornazieri ◽  
Richard L. Doty ◽  
Fábio de Rezende Pinna ◽  
José Marcelo Farfel ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Olfactory Epithelium ◽  
Clinical Symptoms ◽  
Middle Turbinate ◽  
Superior Turbinate ◽  
Significant Difference ◽  
Amyloid Beta Proteins

Objectives: The clinical symptoms of Alzheimer’s disease (AD) are preceded by a long asymptomatic period associated with “silent” deposition of aberrant paired helical filament (PHF)-tau and amyloid-beta proteins in brain tissue. Similar depositions have been reported within the olfactory epithelium (OE), a tissue that can be biopsied in vivo. The degree to which such biopsies are useful in identifying AD is controversial. This postmortem study had 3 main goals: first, to quantify the relative densities of AD-related proteins in 3 regions of the olfactory neuroepithelium, namely, the nasal septum, middle turbinate, and superior turbinate; second, to establish whether such densities are correlated among these epithelial regions as well as with semi-quantitative ratings of general brain cortex pathology; and third, to evaluate correlations between the protein densities and measures of antemortem cognitive function. Methods: Postmortem blocks of olfactory mucosa were obtained from 12 AD cadavers and 24 controls and subjected to amyloid-beta and PHF-tau immunohistochemistry. Results: We observed marked heterogeneity in the presence of the biomarkers of tau and amyloid-beta among the targeted olfactory epithelial regions. No significant difference was observed between the cadavers with AD and the controls regarding the concentration of these proteins in any of these epithelial regions. Only one correlation significant was evident, namely, that between the tau protein densities of the middle and the upper turbinate ( r = .58, P = .002). Conclusion: AD-related biomarker heterogeneity, which has not been previously demonstrated, makes comparisons across studies difficult and throws into question the usefulness of OE amyloid-beta and PHF-tau biopsies in detecting AD.

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