Abbreviation (ISO4): Chinese Journal of Alzheimer's Disease and Related Disorders
Editor in chief: Jun WANG
There have been many different opinions on the pathogenesis of Alzheimer's disease (AD), and the β-amyloid protein (Aβ) theory has always been dominant. However, many treatments targeting on Aβ have had little effect, which has led researchers to re-examine this theory. More and more research findings have made people realize that although the accumulation of Aβ plaques in the brain is closely related to cognitive decline, it may only be a manifestation of AD, not the root cause of this disease. The body's inability to clear the accumulation of proteins including Aβ due to various reasons such as chronic inflammation with brain damage may be a deeper cause of this disease. These important cell functions include endocytosis, macropinocytosis, innate phagocytosis and autophagy, and mitochondria that provide energy to these high-energy consumption applications may be the determining factor affecting these functions. Therefore, simply removing Aβ plaques may have little effect in the treatment of Alzheimer's disease. More efforts should be placed on how to improve essential cell functions like innate phagocytosis and autophagy, as well as to improve mitochondrial function to increase energy production.
Objective: To explore the effect of APOEɛ4 gene carrier status on amyloid deposition in the brain of Alzheimer's disease patients in Chinese population. Methods：A retrospective collection was conducted on 932 cognitively normal individuals and patients diagnosed with mild cognitive impairment or Alzheimer's disease who visited the Memory Clinic of Huashan Hospital affiliated with Fudan University from August 2018 to March 2023. Among them, there were 532 cognitive normal individuals and 400 cognitive impaired individuals, including 211 mild cognitive impairment and 189 Alzheimer's disease patients. All participants were subjected to cognitive assessment, genotype determination, and [18F] Florbetapir PET imaging quantitative analysis of A β deposition in the brain, which is converted into centiloid value. The centiloid value of each group were compared based on cognitive status, APOEɛ4 gene carrying status, gender, and other factors. Performing partial correlation analysis on the centiloid value and cognitive scores of APOEɛ4 gene carrying or non carrying group. Results: The centiloid value of the APOEɛ4 gene carrying group is higher than that of the non carrying group, and the difference is significant (26.7 ± 38.3 vs 3.7 ± 26.6, P<0.001）. In the population with cognitive impaired, the centiloid value of both male and female APOEɛ4 gene carriers were higher than those of non carriers of the same gender (36.2 ± 40.3 vs 9.7 ± 30.7, 39.2 ± 37.5 vs 17.7 ± 38.8, respectively), P<0.001）. However, there is no significant difference in centiloid value between males and females in carriers or non carriers with cognitive impaired (36.2 ± 40.3 vs 39.2 ± 37.5, 9.7 ± 30.7 vs 17.7 ± 38.8, P>0.05）. The difference in centiloid value between the cognitive normal group and the cognitive impaired group is statistically significant (0.2 ± 21.0 vs 23.5 ± 38.6, P<0.001）. In subjects with cognitive impaired or cognitive normal, there is a significant difference in centiloid value between APOEε4 carriers and non carriers (P<0.001).The difference in centiloid value between cognitive impaired and cognitive normal populations is also significant (P<0.001) in APOEε4 gene carriers or non carriers. Under the control of age, education year, and gender, there is a moderate negative correlation between the centiloid value and cognitive scores in both the APOEɛ4 gene carrying and non carrying groups (r=-0.435 and -0.449, respectively,P<0.001）. Conclusion: The deposition of amyloid protein in the brain of APOEɛ4 gene carriers is significantly higher than that of non carriers, and there is a negative correlation between amyloid protein deposition and cognition in APOEɛ4 gene carriers and non carriers.
Objective: The aim of the current study was to explore the specific intrinsic functional connectivity between the the retrosplenial cortex (RSC) and the hippocampal subfields in healthy adults and to characterize the alterations in functional connectivity between the RSC and the hippocampal subfields in amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) patients. Methods: Demographic data, neuropsychological assessments, and resting-state functional magnetic resonance imaging (fMRI) data were collected from 60 AD participants, 60 participants with aMCI, and 60 sex-matched normal controls (NCs). The bilateral RSC, other parts of the posterior cingulate cortex (PCC), and hippocampus (HPC) subfields (including the bilateral cornu ammonis fields (CA1-CA3), the dentate gyrus (DG), and subiculum (SUB)) were selected to investigate functional connectivity alterations in aMCI and AD. Results: Resting-state functional connectivity analysis demonstrated heterogeneity in the degree of connectivity between the HPC and different parts of the total PCC, with considerably greater functional connectivity of the RSC with the HPC compared with other parts of the PCC. Furthermore, the bilateral RSC exhibited widespread intrinsic functional connectivity with all HPC subfields. Compared to the NCs, the aMCI and AD groups showed different magnitudes of decreased functional connectivity between the RSC and the contralateral DG. Additionally, diminished functional connectivity between the left RSC and right DG was correlated with clinical disease severity in aMCI subjects. Conclusion: These findings confirm and extend previous studies suggesting that the RSC is extensively and functionally connected with HPC subfields and that these functional connections are selectively affected in the AD continuum, with prominent disruptions in functional connectivity between the RSC and contralateral DG underpinning episodic memory impairment associated with the disease.
Objective: To investigate the associations of five obesity indicators, body mass index (BMI), body round index (BRI), visceral adiposity index (VAI), lipid accumulation product (LAP), and a body shape index (ABSI), with the risk of mild cognitive impairment (MCI) in middle-aged and older adults. Methods: This cross-sectional study recruited participants from Wuhan and Shiyan cities in Hubei province during 2019 and 2022. After excluding individuals with self-reported dementia or Parkinson's disease and missing general characteristics, a total of 6,917 participants were included in this study. Multiple linear regression and logistic regression models were used to evaluate the associations of body mass index and novel obesity indicators with the cognitive function. Restricted cubic spline model was used to explore the nonlinear relationships between obesity indicators and MCI. Results: Among the 6917 participants in this study, 3338 (48.3%) were males and 3579 (51.7%) were females. A total of 670 (9.7%) participants were identified as MCI. Increased BRI and ABSI were associated with decreased MMSE score and raised MCI risk (P trend < 0.001). After adjusting for confounding, compared to the Q1 subgroup, individuals in the BRI, ABSI and LAP Q4 subgroup respectively showed increased MCI risk [OR (95% CI)=1.58 (1.23,2.03), 2.54 (1.68, 3.86), 1.38 (1.08, 1.76)]. RCS confirmed the linear dose-response relationships of BRI and ABSI with MCI risk (both P for non-linear associations were > 0.05). However, BMI and VAI were not found to be correlated with MCI risk. Conclusion: High BRI, ABSI and LAP may be risk factors for cognitive decline, and BRI and ABSI may present a potential dose-response relationship with MCI risk.
Objective: To investigate the characteristic of sporadic Creutzfeldt-Jakob disease(sCJD), improve the knowledge of sCJD for clinicians. Methods: We collected the clinical data, brain neuroimages and laboratory test results of a case of sCJD and reviewed relative articles. Results: The patient showed limb rigidity, involuntary movements, myoclonic jerks, speech disorders, rapidly progressive cognitive impairment, and later autonomic dysfunction, and passed away 8 months after the onset. Conclusion: The early symptoms of sCJD are atypical, varied and heterogeneous, with a high fatality rate. The diagnosis of CJD requires attention to distinguishing it from various diseases, and dynamic examination of cerebrospinal fluid, brain MRI, electroencephalogram, and even biopsy to avoid misdiagnosis and missed diagnosis.
Recent studies have shown that Kallikrein-related peptidases (KLKs) play crucial roles in the pathological progression of Alzheimer's disease (AD). This review systematically summarizes the latest research advances in AD-related KLKs (KLK1, KLK6, KLK7, KLK8, and KLK10). Studies have revealed that KLK6 affects amyloid-β (Aβ) generation by inhibiting α-secretase and enhancing γ-secretase activity; KLK7, as an Aβ-degrading enzyme secreted by astrocytes, shows accelerated Aβ deposition in AD model mice when deficient; KLK8 influences the PI3K/Akt/GSK-3β signaling pathway, leading to decreased Akt phosphorylation and increased GSK-3β expression, thereby promoting Tau protein hyperphosphorylation, with significantly higher expression levels observed in female AD patients compared to males. Furthermore, KLKs impair blood-brain barrier function through mechanisms including extracellular matrix protein cleavage and reduction of endothelial cell inflammation. Meanwhile, KLK6 and KLK8 exhibit significantly elevated expression levels in the cerebrospinal fluid and blood of AD patients, suggesting their potential value as biomarkers. A deeper understanding of KLKs' mechanisms in AD will provide new insights into the early diagnosis and treatment of the disease.
Vascular dementia (VaD) is a severe syndrome of cognitive impairment caused by ischemic stroke, hemorrhagic stroke, and cerebrovascular lesions that cause hypoperfusion of memory, cognitive, and behavioral brain regions. Among the types of dementia, VaD is the second most common cause after Alzheimer's disease, but the pathogenesis of VaD is still unclear. Astrocytes are the most abundant glial cells in the central nervous system.Astrocytes have the ability to produce and release specific neurotransmitters, and express corresponding neurotransmitter receptors,which can respond to a variety of neuroactive substances.In recent years, a large number of studies have been carried out on the role of astrocytes in the central nervous system (CNS), and this article reviews the current role and mechanism of astrocytes in the progression of VaD based on the research background and research significance.We hope to provide a useful reference for understanding the pathogenesis of VaD and exploring new treatment methods and bring new breakthroughs in the treatment of clinical VaD.
Objective: Holmes tremor (HT) is a rare movement disorder. HT may also be associated with other neurological symptoms, including cognitive dysfunction. This study aims to investigate the pathophysiological mechanisms, diagnostic approaches, and therapeutic strategies for HT, thereby providing guidance for clinical management. Methods: The diagnosis of HT primarily relies on clinical features and neuroimaging techniques, such as MRI. Treatment options include pharmacological interventions (e.g., levodopa, trihexyphenidyl) and surgical approaches (e.g., deep brain stimulation, thalamotomy). A systematic review of the literature was conducted to summarize the clinical features, pathophysiological mechanisms, and treatment outcomes of HT. Results: HT symptoms typically emerge between 4 weeks and 2 years after neurological injury, associated with abnormal synaptic reorganization and collateral axonal sprouting following neuronal damage. The efficacy of pharmacological treatments varies among individuals, with levodopa showing effectiveness in approximately 54% of patients, though overall efficacy remains limited. Other medications, such as antiepileptic drugs and dopamine agonists, are also commonly used, but their effectiveness can be highly variable, with some patients showing poor response to these drugs. Surgical interventions, including deep brain stimulation, thalamotomy, lesionectomy of the original pathological focus, and ablation of specific nuclei, have demonstrated some efficacy but exhibit individual variability. There is currently no unified treatment consensus, and large-scale multicenter studies validating the long-term outcomes of novel therapies are lacking. Conclusion: The treatment of HT remains challenging, and its pathophysiological mechanisms are not yet fully understood. Future research should further investigate the pathophysiological mechanisms of HT, particularly its relationship with cognitive dysfunction, and optimize treatment strategies. Conducting multicenter studies to validate the long-term efficacy of novel therapies holds promise for improving the quality of life and prognosis of HT patients.
Alzheimer's disease has become a great concern in the current aging society. In order to better treat this disease, it is crucial to study and understand its pathogenic mechanisms. Equally important is how to detect Alzheimer's disease early and more accurately. Here, we summarized the pathogenic mechanisms of Alzheimer's disease and compared its different detection methods.
Alzheimer's disease (AD) and osteoporosis (OP) are both age-related degenerative diseases,which mainly occur in the elderly population over the age of 60, and are becoming an increasingly common combination in the aging population. It has been proved that a variety of factors can stimulate and accelerate the occurrence of AD and OP in clinical practice. This review mainly studies the common pathogenesis of AD and OP, and discusses the pathogenesis factors such as vitamin D and vitamin K levels, signaling pathways, apolipoprotein and neuroinflammation in AD mouse models. In addition,potential treatments for these two diseases are described.
ISSN 2096-5516 (Print)
Started from 2018
Published by: China Association for Alzheimer’s Disease
