scholarly journals Involvement of Cholinergic, Adrenergic, and Glutamatergic Network Modulation with Cognitive Dysfunction in Alzheimer’s Disease

2021 ◽  
Vol 22 (5) ◽  
pp. 2283
Author(s):  
Yu-Jung Cheng ◽  
Chieh-Hsin Lin ◽  
Hsien-Yuan Lane
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Early Stage ◽  
Amyloid Β ◽  
Tau Proteins ◽  
And Oxidative Stress

Alzheimer’s disease (AD), the most common cause of dementia, is a progressive neurodegenerative disease. The number of AD cases has been rapidly growing worldwide. Several the related etiological hypotheses include atypical amyloid β (Aβ) deposition, neurofibrillary tangles of tau proteins inside neurons, disturbed neurotransmission, inflammation, and oxidative stress. During AD progression, aberrations in neurotransmission cause cognitive decline—the main symptom of AD. Here, we review the aberrant neurotransmission systems, including cholinergic, adrenergic, and glutamatergic network, and the interactions among these systems as they pertain to AD. We also discuss the key role of N-methyl-d-aspartate receptor (NMDAR) dysfunction in AD-associated cognitive impairment. Furthermore, we summarize the results of recent studies indicating that increasing glutamatergic neurotransmission through the alteration of NMDARs shows potential for treating cognitive decline in mild cognitive impairment or early stage AD. Future studies on the long-term efficiency of NMDA-enhancing strategies in the treatment of AD are warranted.

The Impact of Amyloid-β or Tau on Cognitive Change in the Presence of Severe Cerebrovascular Disease

2020 ◽  
Vol 78 (2) ◽  
pp. 573-585
Author(s):  
Hyemin Jang ◽  
Hee Jin Kim ◽  
Yeong Sim Choe ◽  
Soo-Jong Kim ◽  
Seongbeom Park ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Interaction Effect ◽  
Significant Interaction ◽  
Amyloid Β ◽  
Cognitive Change ◽  
Significant Interaction Effect ◽  
The Impact

Background: As Alzheimer’s disease (AD) and cerebral small vessel disease (CSVD) commonly coexist, the interaction between two has been of the considerable interest. Objective: We determined whether the association of Aβ and tau with cognitive decline differs by the presence of significant CSVD. Methods: We included 60 subcortical vascular cognitive impairment (SVCI) from Samsung Medical Center and 82 Alzheimer’s disease-related cognitive impairment (ADCI) from ADNI, who underwent Aβ (florbetaben or florbetapir) and tau (flortaucipir, FTP) PET imaging. They were retrospectively assessed for 5.0±3.9 and 5.6±1.9 years with Clinical Dementia Rating-sum of boxes (CDR-SB)/Mini-Mental State Examination (MMSE). Mixed effects models were used to investigate the interaction between Aβ/tau and group on CDR-SB/MMSE changes. Results: The frequency of Aβ positivity (45% versus 54.9%, p = 0.556) and mean global FTP SUVR (1.17±0.21 versus 1.16±0.17, p = 0.702) were not different between the two groups. We found a significant interaction effect of Aβ positivity and SVCI group on CDR-SB increase/MMSE decrease (p = 0.013/p < 0.001), and a significant interaction effect of global FTP uptake and SVCI group on CDR-SB increase/MMSE decrease (p < 0.001 and p = 0.030). Finally, the interaction effects of regional tau and group were prominent in the Braak III/IV (p = 0.001) and V/VI (p = 0.003) not in Braak I/II region (p = 0.398). Conclusion: The association between Aβ/tau and cognitive decline is stronger in SVCI than in ADCI. Therefore, our findings suggested that Aβ positivity or tau burden (particularly in the Braak III/IV or V/VI regions) and CSVD might synergistically affect cognitive decline.

scholarly journals A Strategy for Identifying the Risk of Developing Alzheimer's Disease From Healthy Controls: Distance to Novelty Detection Boundary

2020 ◽  
Author(s):  
Jiangbing Mao ◽  
Qinyong Ye ◽  
Hongqing Yang ◽  
Magda Bucholc ◽  
Shuo Liu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Early Stage ◽  
Novelty Detection ◽  
Imaging Biomarkers ◽  
Support Vector ◽  
Support Vector Data Description ◽  
Healthy Controls

Abstract Background:Machine learning (ML) techniques are expected to tackle the problem of the high prevalence of Alzheimer’s disease (AD) we are facing worldwide. However, few studies of novelty detection (ND), a typical ML technique for safety-critical systems especially in healthcare, were engaged for identifying the risk of developing cognitive impairment from healthy controls (HC) population.Materials and Methods: Two independent datasets were used for this study, including the Australian Imaging Biomarkers and Lifestyle Study of Ageing (AIBL) and the Fujian Medical University Union Hospital (FMUUH), China datasets. Multiple feature selection methods were applied to identify the most relevant features for predicting the severity of AD. Four easily interpretable ND algorithms, including k nearest neighbor, Mixture of Gaussian (MoG), KMEANS, and support vector data description were used to construct predictive models. The models were visualized by drawing their decision boundaries tightly surrounding the HC data. A distance to boundary (DtB) strategy was proposed to differentiate individuals with mild cognitive impairment (MCI) and AD from HC. Results: The best overall MCI&AD detection performance in both AIBL and FMUUH was obtained on the cognitive and functional assessments (CFA) modality only using MoG-based ND with AUC of 0.8757 and 0.9443, respectively. The highest sensitivity of MCI was presented by using a combination of CFA and brain imaging modality. The DTB value reflects the risk of developing cognitive impairment for HC and the dementia severity of MCI/AD.Conclusions: Our findings suggest that applying some non-invasive and cost-effective features can significantly detect cognitive decline in an early stage. The visualized decision boundary and the proposed DtB strategy illustrated the severity of cognitive decline of potential MCI&AD patients in an early stage. The results would help inform future guidelines for developing a clinical decision-making support system aiming at an early diagnosis and prognosis of MCI&AD.

scholarly journals Role of Amyloid-β and Tau Proteins in Alzheimer’s Disease: Confuting the Amyloid Cascade

2019 ◽  
Vol 68 (1) ◽  
pp. 415-415 ◽  
Author(s):  
Walter Gulisano ◽  
Daniele Maugeri ◽  
Marian A. Baltrons ◽  
Mauro Fà ◽  
Arianna Amato ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Tau Proteins ◽  
Amyloid Cascade

scholarly journals Role of Amyloid-β and Tau Proteins in Alzheimer’s Disease: Confuting the Amyloid Cascade

2018 ◽  
Vol 64 (s1) ◽  
pp. S611-S631 ◽  
Author(s):  
Walter Gulisano ◽  
Daniele Maugeri ◽  
Marian A. Baltrons ◽  
Mauro Fà ◽  
Arianna Amato ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Tau Proteins ◽  
Amyloid Cascade

Vascular cognitive impairment and Alzheimer’s disease: role of cerebral hypoperfusion and oxidative stress

2012 ◽  
Vol 385 (10) ◽  
pp. 953-959 ◽  
Author(s):  
Hyun Ah Kim ◽  
Alyson A. Miller ◽  
Grant R. Drummond ◽  
Amanda G. Thrift ◽  
Thiruma V. Arumugam ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Vascular Cognitive Impairment ◽  
Cerebral Hypoperfusion ◽  
And Oxidative Stress

scholarly journals Reduced Levels of Hsa-mir-342-5p in Plasma Are Associated With Worse Cognitive Evolution in Patients With Mild Alzheimer’s Disease

2020 ◽  
Author(s):  
Farida Dakterzada ◽  
Iván David Benítez ◽  
Adriano Targa ◽  
Albert Lladó ◽  
Gerard Torres ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Differentially Expressed ◽  
Differentially Expressed Mirnas ◽  
Rate Of Decline ◽  
Plasma Mirnas

Abstract Background: Progressive cognitive decline is the most relevant clinical symptom of Alzheimer’s disease (AD). However, the rate of cognitive decline is highly variable between patients. Synaptic deficits are the neuropathological event most correlated with cognitive impairment in AD. Considering the important role of microRNAs (miRNAs) in regulating synaptic plasticity, our objective was to identify the plasma miRNAs associated with the rate of cognitive decline in patients with mild AD.Methods: To discover the miRNAs related to the rate of cognitive impairment, we analysed 754 plasma miRNAs from 19 women diagnosed with mild AD using TaqMan low-density array cards. The patients were grouped based on the rate of decline in the MMSE score after two years (<4 points (N=11) and ≥ 4 points (N=8)). The differentially expressed miRNAs between the two groups were validated in an independent cohort of men and women (N=53) with mild AD using RT-qPCR.Results: In the discovery cohort, 17 miRNAs were differentially expressed according to the fold change between patients with faster declines in cognition and those with slower declines. miR-342-5p demonstrated differential expression between the groups and a good correlation with the rate of cognitive decline in the validation cohort (r=-0.28; p=0.026). This miRNA had a lower expression level in patients who suffered from more severe decline than in those who were cognitively more stable after two years (p=0.049).Conclusion: Lower levels of miR-342-5p in plasma were associated with faster cognitive decline in patients with mild AD after two years of follow-up.

scholarly journals Exercise Intervention Associated with Cognitive Improvement in Alzheimer’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Meng Ying Cui ◽  
Yang Lin ◽  
Ji Yao Sheng ◽  
Xuewen Zhang ◽  
Ran Ji Cui
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Healthy Aging ◽  
Exercise Intervention ◽  
Early Stage ◽  
Functional Decline ◽  
Cost Effective ◽  
Cognitive Improvement

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with the syndrome of cognitive and functional decline. Pharmacotherapy has always been in a dominant position for the treatment of AD. However, in most cases, drug therapy is accompanied with clinical delays when older adults have suffered from cognitive decline in episodic memory, working memory, and executive function. On the other hand, accumulating evidence suggests that exercise intervention may ameliorate the progression of cognitive impairment in aging ones while the standard strategy is lacking based on different levels of cognitive decline especially in mild cognitive impairment (MCI) and AD. MCI is the preclinical stage of AD in which neurodegeneration may be reversed via neuroplasticity. Therefore, taking exercise intervention in the early stage of MCI and healthy aging at the risk of AD could slow down the process of cognitive impairment and provide a promising cost-effective nonpharmacological therapy to dementia.

Long-Term Exposure to PM10 and in vivo Alzheimer’s Disease Pathologies

2021 ◽  
Author(s):  
Jun Ho Lee ◽  
Min Soo Byun ◽  
Dahyun Yi ◽  
Kang Ko ◽  
So Yeon Jeon ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Amyloid Β ◽  
Aerodynamic Diameter ◽  
Cognitively Normal ◽  
Study Population

Background: Previous studies indicated an association between Alzheimer’s disease (AD) dementia and air particulate matter (PM) with aerodynamic diameter <10 μm (PM10), as well as smaller PM. Limited information, however, is available for the neuropathological links underlying such association. Objective: This study aimed to investigate the relationship between long-term PM10 exposure and in vivo pathologies of AD using multimodal neuroimaging. Methods: The study population consisted of 309 older adults without dementia (191 cognitively normal and 118 mild cognitive impairment individuals), who lived in Republic of Korea. Participants underwent comprehensive clinical assessments, 11C-Pittsburg compound B (PiB) positron emission tomography (PET), and magnetic resonance imaging scans. A subset of 78 participants also underwent 18F-AV-1451 tau PET evaluation. The mean concentration of PM with aerodynamic diameter <10 μm over the past 5 years (PM10mean) collected from air pollution surveillance stations were matched to each participant’s residence. Results: In this non-demented study population, of which 62% were cognitively normal and 38% were in mild cognitive impairment state, exposure to the highest tertile of PM10mean was associated with increased risk of amyloid-β (Aβ) positivity (odds ratio 2.19, 95% confidence interval 1.13 to 4.26) even after controlling all potential confounders. In contrast, there was no significant associations between PM10mean exposure and tau accumulation. AD signature cortical thickness and white matter hyperintensity volume were also not associated with PM10mean exposure. Conclusion: The findings suggest that long-term exposure to PM10 may contribute to pathological Aβ deposition.

scholarly journals The Role of Lysosomes in a Broad Disease-Modifying Approach Evaluated across Transgenic Mouse Models of Alzheimer’s Disease and Parkinson’s Disease and Models of Mild Cognitive Impairment

2019 ◽  
Vol 20 (18) ◽  
pp. 4432 ◽  
Author(s):  
Jeannie Hwang ◽  
Candice M. Estick ◽  
Uzoma S. Ikonne ◽  
David Butler ◽  
Morgan C. Pait ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Amyloid Β ◽  
Age Related ◽  
Disease Modifying

Many neurodegenerative disorders have lysosomal impediments, and the list of proposed treatments targeting lysosomes is growing. We investigated the role of lysosomes in Alzheimer’s disease (AD) and other age-related disorders, as well as in a strategy to compensate for lysosomal disturbances. Comprehensive immunostaining was used to analyze brains from wild-type mice vs. amyloid precursor protein/presenilin-1 (APP/PS1) mice that express mutant proteins linked to familial AD. Also, lysosomal modulation was evaluated for inducing synaptic and behavioral improvements in transgenic models of AD and Parkinson’s disease, and in models of mild cognitive impairment (MCI). Amyloid plaques were surrounded by swollen organelles positive for the lysosome-associated membrane protein 1 (LAMP1) in the APP/PS1 cortex and hippocampus, regions with robust synaptic deterioration. Within neurons, lysosomes contain the amyloid β 42 (Aβ42) degradation product Aβ38, and this indicator of Aβ42 detoxification was augmented by Z-Phe-Ala-diazomethylketone (PADK; also known as ZFAD) as it enhanced the lysosomal hydrolase cathepsin B (CatB). PADK promoted Aβ42 colocalization with CatB in lysosomes that formed clusters in neurons, while reducing Aβ deposits as well. PADK also reduced amyloidogenic peptides and α-synuclein in correspondence with restored synaptic markers, and both synaptic and cognitive measures were improved in the APP/PS1 and MCI models. These findings indicate that lysosomal perturbation contributes to synaptic and cognitive decay, whereas safely enhancing protein clearance through modulated CatB ameliorates the compromised synapses and cognition, thus supporting early CatB upregulation as a disease-modifying therapy that may also slow the MCI to dementia continuum.

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