Structural MR Imaging in the Diagnosis of Alzheimer's Disease and Other Neurodegenerative Dementia: Current Imaging Approach and Future Perspectives

Frontotemporal dementia (FTD) is a common neurodegenerative dementia syndrome. Compulsive behaviors frequently occur in FTD and may be presenting symptoms of this disorder. This study evaluated compulsive behaviors as presenting symptoms in 29 patients with FTD compared to 48 patients with Alzheimer's disease (AD) enrolled in the UCLA Alzheimer's Disease Center. The FTD patients met the Lund and Manchester criteria for FTD and had predominant frontal hypoperfusion on single-photon emission computer tomography neuroimaging. The AD patients met National Institute of Neurological and Communicative Disorders-Alzheimer's Disease and Related Disorders criteria for clinically probable AD. Compulsive behaviors occurred in 11 FTD patients (38%) versus 5 AD patients (10%) (χ2 = 6.73, P < .01). This difference persisted after controlling for the younger age of the FTD group. There was a range of compulsive behaviors, with the most frequent being repetitive checking activities. Compulsive behaviors are common presenting symptoms among FTD patients and may result from an inability to inhibit urges to perform compulsive movements from damage to frontal-striatal circuits.

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Pharmacotherapy of Alzheimer's Disease: Current State and Future Perspectives

Frontiers in Drug Design & Discovery ◽

10.2174/9781608058228114060003 ◽

2014 ◽

pp. 3-39

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Future Perspectives ◽

Current State

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pLG72 levels increase in early phase of Alzheimer’s disease but decrease in late phase

Scientific Reports ◽

10.1038/s41598-019-49522-1 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 5

Author(s):

Chieh-Hsin Lin ◽

Chih-Chiang Chiu ◽

Chiung-Hsien Huang ◽

Hui-Ting Yang ◽

Hsien-Yuan Lane

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amino Acid ◽

Early Phase ◽

Late Phase ◽

Acid Oxidase ◽

Matched Cohort ◽

Amino Acid Oxidase ◽

Gender And Age ◽

Neurodegenerative Dementia

Abstract pLG72, named as D-amino acid oxidase activator (although it is not an activator of D-amino acid oxidase demonstrated by later studies), in mitochondria has been regarded as an important modulator of D-amino acid oxidase that can regulate the N-methyl-D-aspartate receptor (NMDAR). Both oxidative stress in mitochondria and NMDAR neurotransmission play essential roles in the process of neurodegenerative dementia. The aim of the study was to investigate whether pLG72 levels changed with the severity of neurodegenerative dementia. We enrolled 376 individuals as the overall cohort, consisting of five groups: healthy elderly, amnestic mild cognitive impairment [MCI], mild Alzheimer’s disease [AD], moderate AD, and severe AD. pLG72 levels in plasma were measured using Western blotting. The severity of cognitive deficit was principally evaluated by Clinical Dementia Rating Scale. A gender- and age- matched cohort was selected to elucidate the effects of gender and age. pLG72 levels increased in the MCI and mild AD groups when compared to the healthy group. However, pLG72 levels in the moderate and severe AD groups were lower than those in the mild AD group. D-serine level and D- to total serine ratio were significantly different among the five groups. L-serine levels were correlated with the pLG72 levels. The results in the gender- and age- matched cohort were similar to those of the overall cohort. The finding supports the hypothesis of NMDAR hypofunction in early-phase dementia and NMDAR hyperfunction in late-phase dementia. Further studies are warranted to test whether pLG72 could reflect the function of NMDAR.

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The Role of APP O-Glycosylation in Alzheimer’s Disease

Biomolecules ◽

10.3390/biom10111569 ◽

2020 ◽

Vol 10 (11) ◽

pp. 1569

Author(s):

Keiko Akasaka-Manya ◽

Hiroshi Manya

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Senile Plaque ◽

Amyloid Β ◽

Pathological Feature ◽

People With Dementia ◽

New Findings ◽

Neurodegenerative Dementia ◽

Aβ Production

The number of people with dementia is increasing rapidly due to the increase in the aging population. Alzheimer’s disease (AD) is a type of neurodegenerative dementia caused by the accumulation of abnormal proteins. Genetic mutations, smoking, and several other factors have been reported as causes of AD, but alterations in glycans have recently been demonstrated to play a role in AD. Amyloid-β (Aβ), a cleaved fragment of APP, is the source of senile plaque, a pathological feature of AD. APP has been reported to undergo N- and O-glycosylation, and several Polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts) have been shown to have catalytic activity for the transfer of GalNAc to APP. Since O-glycosylation in the proximity of a cleavage site in many proteins has been reported to be involved in protein processing, O-glycans may affect the cleavage of APP during the Aβ production process. In this report, we describe new findings on the O-glycosylation of APP and Aβ production.

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Nanobiosensors for Non-Amyloidbeta-Tau Biomarkers as Advanced Reporters of Alzheimer’s Disease

Diagnostics ◽

10.3390/diagnostics10110913 ◽

2020 ◽

Vol 10 (11) ◽

pp. 913

Author(s):

Le Minh Tu Phan ◽

Thi Xoan Hoang ◽

Thuy Anh Thu Vo ◽

Jae Young Kim ◽

Sang-Myung Lee ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Clinical Trials ◽

Therapeutic Response ◽

Accurate Diagnosis ◽

Clinical Severity ◽

Future Perspectives ◽

Comprehensive Management ◽

Diagnosis And Prognosis ◽

Sensitivity Specificity

Emerging nanomaterials providing benefits in sensitivity, specificity and cost-effectiveness are being widely investigated for biosensors in the application of Alzheimer’s disease (AD) diagnosis. Core biomarkers amyloid-beta (Aβ) and Tau have been considered as key neuropathological hallmarks of AD. However, they did not sufficiently reflect clinical severity and therapeutic response, proving the difficulty of the Aβ- and Tau-targeting therapies in clinical trials. In recent years, there has still been a shortage of sensors for non-Aβ-Tau pathophysiological biomarkers that serve as advanced reporters for the early diagnosis of AD, predict AD progression, and monitor the treatment response. Nanomaterial-based sensors measuring multiple non-Aβ-Tau biomarkers could improve the capacity of AD progression characterization and supervised treatment, facilitating the comprehensive management of AD. This is the first review to principally represent current nanobiosensors for non-Aβ-Tau biomarker and that strategically deliberates future perspectives on the merit of non-Aβ-Tau biomarkers, in combination with Aβ and Tau, for the accurate diagnosis and prognosis of AD.

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