The Latest Articles on Early Alzheimer's Disease
Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.
This week, we would like to share several latest articles on Early Alzheimer’s Disease.
Title: Converging links between adult-onset neurodegenerative Alzheimer's disease and early life neurodegenerative neuronal ceroid lipofuscinosis?
Authors: Marcel Klein, Guido Hermey
Type: Review
Abstract:
Evidence from genetics and from analyzing cellular and animal models have converged to suggest links between neurodegenerative disorders of early and late life. Here, we summarize emerging links between the most common late life neurodegenerative disease, Alzheimer's disease, and the most common early life neurodegenerative diseases, neuronal ceroid lipofuscinoses. Genetic studies reported an overlap of clinically diagnosed Alzheimer's disease and mutations in genes known to cause neuronal ceroid lipofuscinoses. Accumulating data strongly suggest dysfunction of intracellular trafficking mechanisms and the autophagy-endolysosome system in both types of neurodegenerative disorders. This suggests shared cytopathological processes underlying these different types of neurodegenerative diseases. A better understanding of the common mechanisms underlying the different diseases is important as this might lead to the identification of novel targets for therapeutic concepts, the transfer of therapeutic strategies from one disease to the other and therapeutic approaches tailored to patients with specific mutations. Here, we review dysfunctions of the endolysosomal autophagy pathway in Alzheimer's disease and neuronal ceroid lipofuscinoses and summarize emerging etiologic and genetic overlaps.
Access this article: https://pubmed.ncbi.nlm.nih.gov/36571343/
Title: Salvianolic acid B ameliorates retinal deficits in an early-stage Alzheimer's disease mouse model through downregulating BACE1 and Aβ generation
Authors: Meng-Dan Wang, Shuo Zhang, Xing-Yang Liu, Pan-Pan Wang, Yi-Fan Zhu, Jun-Rong Zhu, Chong-Shan Lv, Shi-Ying Li, Sui-Feng Liu, Lei Wen
Type: Research article
Abstract:
Alzheimer's disease (AD) is a neurodegenerative disease with subtle onset, early diagnosis remains challenging. Accumulating evidence suggests that the emergence of retinal damage in AD precedes cognitive impairment, and may serve as a critical indicator for early diagnosis and disease progression. Salvianolic acid B (Sal B), a bioactive compound isolated from the traditional Chinese medicinal herb Salvia miltiorrhiza, has been shown promise in treating neurodegenerative diseases, such as AD and Parkinson's disease. In this study we investigated the therapeutic effects of Sal B on retinopathy in early-stage AD. One-month-old transgenic mice carrying five familial AD mutations (5×FAD) were treated with Sal B (20 mg·kg-1·d-1, i.g.) for 3 months. At the end of treatment, retinal function and structure were assessed, cognitive function was evaluated in Morris water maze test. We showed that 4-month-old 5×FAD mice displayed distinct structural and functional deficits in the retinas, which were significantly ameliorated by Sal B treatment. In contrast, untreated, 4-month-old 5×FAD mice did not exhibit cognitive impairment compared to wild-type mice. In SH-SY5Y-APP751 cells, we demonstrated that Sal B (10 μM) significantly decreased BACE1 expression and sorting into the Golgi apparatus, thereby reducing Aβ generation by inhibiting the β-cleavage of APP. Moreover, we found that Sal B effectively attenuated microglial activation and the associated inflammatory cytokine release induced by Aβ plaque deposition in the retinas of 5×FAD mice. Taken together, our results demonstrate that functional impairments in the retina occur before cognitive decline, suggesting that the retina is a valuable reference for early diagnosis of AD. Sal B ameliorates retinal deficits by regulating APP processing and Aβ generation in early AD, which is a potential therapeutic intervention for early AD treatment.
Access this article: https://pubmed.ncbi.nlm.nih.gov/37420104/
Title: ADAM10 as a biomarker for Alzheimer's disease: A systematic review
Authors: M.P. Oliveira Monteiro e Pereira de Almeida, R. Valle Pedroso, M. Mantellatto Grigoli, T. Vicente Silva, P.R. Manzine, M.R. Cominetti
Type: Review
Abstract:
Background:
Studies have shown that A Disintegrin and Metalloproteinase 10 (ADAM10) is the main α-secretase in the non-amyloidogenic cleavage of the amyloid precursor protein (APP), avoiding the production of amyloid-β peptide (Aβ), one of the pathological hallmarks of Alzheimer's disease (AD).
Objective:
To investigate ADAM10 from cerebrospinal fluid (CSF) and plasma/serum as a potential biomarker for AD.
Methods:
A systematic review was carried out in the MEDLINE/PubMed, Web of Science, Embase, and Scopus databases using the terms and Boolean operators: “Alzheimer” AND “ADAM10” AND “biomarker”. Citation searching was also adopted. The inclusion criteria were original studies of ADAM10 in blood or CSF in patients with AD. The risk of bias was assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. The analysis methods were registered in the PROSPERO database (#CRD42021274239).
Results:
Of the 97 records screened, 17 were included. There is strong evidence for lower levels of ADAM10 in platelets of persons with AD compared to cognitively healthy participants. On the other hand, higher levels of ADAM10 were found in plasma. Regarding CSF, controversial results were found with lower and higher levels of ADAM10 in persons with AD compared to healthy older adults. The differences may be due to diverse reasons, including different sample collection and processing and different antibodies, highlighting the importance of standardizing the experiments and choosing the appropriate antibodies for ADAM10 detection.
Conclusion:
Evidence shows that ADAM10 levels are altered in platelets, plasma, serum, and CSF of individuals with AD. The alteration was evident in all stages of the disease, and therefore, the protein may represent a complementary biomarker for the disease. However, more studies must be performed to establish cut-off values for ADAM10 levels to discriminate AD participants from cognitively unimpaired older adults.
Access this article: https://doi.org/10.1016/j.neurol.2023.04.002
Title: EAD-DNN: Early Alzheimer's disease prediction using deep neural networks
Authors: Preethi Thangavel, Yuvaraj Natarajan, K.R. Sri Preethaa
Type: Research article
Abstract:
Early Alzheimer’s disease (EAD) diagnosis enables individuals to take preventative actions before irreversible brain damage occurs. Memory and thinking skills get worse in alzheimer disease, making it hard to do basic things. The abnormal buildup of amyloid and tau proteins in and around brain cells is thought to cause it. When amyloid builds up, it forms plaques around brain cells. Inside brain cells, tau tangles form when it accumulates. Healthy brain cells are damaged by the tangles and plagues, which causes them to shrink. The hippocampus, a part of the brain that aids in memory formation, appears to be the location of this damage. There are currently no methods that give the most accurate results and suggestions. With the methods we have now, alzheimer disease is not found early. So, we said that the Early Alzheimer’s disease - Deep Neural Network (EAD-DNN) method has found a way to predict alzheimer disease earlier. The Magnetic Resonance Imaging (MRI) dataset in the Comma Separated Value (CSV) format has been used by the EAD-DNN method. Convolutional Neural Network (CNN), the deep Residual Network (ResNet) has been used to train the MRI image dataset. This ResNet model can get more information from network levels with the help of Deep ResNet.The modified adam optimization has selected the best feature information from MRI scans of alzheimer patients and transferred it to another area while keeping the most important data. Using the EAD-DNN approach, a multi-class classification has been carried out. The extensive experiments show that the suggested method can achieve an accuracy rate of 98%.
Access this article: https://doi.org/10.1016/j.bspc.2023.105215
Title: Effects of different levodopa doses on blood pressure in older patients with early and middle stages of Parkinson's disease
Authors: Dan Su, Xiaojun Zhang, Yanling Su, Piu Chan, Erhe Xu
Type: Research article
Objective:
Levodopa is the first-line treatment for patients with Parkinson's disease (PD). However, only a few studies have focused on the tolerance of this drug in older patients with PD in the early and middle stages. Therefore, this study aimed to explore the effects of different levodopa doses on blood pressure (BP) in this subpopulation.
Methods:
This cohort analysis enrolled 83 patients. The levodopa challenge test was used to evaluate drug responsiveness. After at least 12 h following anti-PD drug discontinuation, patients’ BPs were measured in a lying position, after 1 min standing, and after 3 min standing, in “off state” and best “on state.”
Results:
BP in the 250 mg and 375 mg levodopa/benserazide groups decreased significantly in the lying and standing positions. The 3-min standing-position systolic BP was significantly influenced by the dose of levodopa/benserazide. However, no statistical change was observed in the 125 mg group. The postural-mediated systolic BP disparity was significant at 3 min in the upright position. Nineteen (incidence, 22.9%) and Twenty-five patients (incidence, 30.1%) developed complications of orthostatic hypotension (OH) in the “off state” and best “on state,” respectively. Mild cognitive impairment was a risk factor for OH occurrence in the “off state.” The OH occurrence in the best “on state” was associated with OH in the “off state” and urinary incontinence.
Conclusion:
Our findings suggest that 250 mg or more of levodopa/benserazide could significantly reduce BP and orthostatic effect in older patients with PD in the early and middle stages. Therefore, they should routinely monitor their BP.
Access this article: https://doi.org/10.1016/j.heliyon.2023.e17876
