skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Explore Research Products in the PAR
It may take a few hours for recently added research products to appear in PAR search results.


  • NSF Public Access
  • Search Results
  • Levels of Angiotensin-Converting Enzyme and Apolipoproteins Are Associated with Alzheimer’s Disease and Cardiovascular Diseases
Title: Levels of Angiotensin-Converting Enzyme and Apolipoproteins Are Associated with Alzheimer’s Disease and Cardiovascular Diseases
Angiotensin-converting enzyme-1 (ACE1) and apolipoproteins (APOs) may play important roles in the development of Alzheimer’s disease (AD) and cardiovascular diseases (CVDs). This study aimed to examine the associations of AD, CVD, and endocrine-metabolic diseases (EMDs) with the levels of ACE1 and 9 APO proteins (ApoAI, ApoAII, ApoAIV, ApoB, ApoCI, ApoCIII, ApoD, ApoE, and ApoH). Non-Hispanic white individuals including 109 patients with AD, 356 mild cognitive impairment (MCI), 373 CVD, 198 EMD and controls were selected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. Multivariable general linear model (GLM) was used to examine the associations. ApoE ε4 allele was associated with AD, as well as ApoAIV, ApoB and ApoE proteins, but not associated with CVD and EMD. Both AD and CVD were associated with levels of ACE1, ApoB, and ApoH proteins. AD, MCI and EMD were associated with levels of ACE1, ApoAII, and ApoE proteins. This is the first study to report associations of ACE1 and several APO proteins with AD, MCI, CVD and EMD, respectively, including upregulated and downregulated protein levels. In conclusion, as specific or shared biomarkers, the levels of ACE1 and APO proteins are implicated for AD, CVD, EMD and ApoE ε4 allele. Further studies are required for validation to establish reliable biomarkers for these health conditions.  more » « less
Award ID(s):
1920920
PAR ID:
10336045
Author(s) / Creator(s):
; ; ; ; ;
Date Published:
Journal Name:
Cells
Volume:
11
Issue:
1
ISSN:
2073-4409
Page Range / eLocation ID:
29
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; ; (, International Journal of Molecular Sciences)
    Alzheimer’s disease (AD) presents significant challenges in clinical practice due to its heterogeneous manifestation and variable progression rates. This work develops a comprehensive anatomical staging framework to predict progression from mild cognitive impairment (MCI) to AD. Using the ADNI database, the scalable Subtype and Stage Inference (s-SuStaIn) model was applied to 118 neuroanatomical features from cognitively normal (n = 504) and AD (n = 346) participants. The framework was validated on 808 MCI participants through associations with clinical progression, CSF and FDG-PET biomarkers, and neuropsychiatric measures, while adjusting for common confounders (age, gender, education, and APOE ε4 alleles). The framework demonstrated superior prognostic accuracy compared to traditional risk assessment (C-index = 0.73 vs. 0.62). Four distinct disease subtypes showed differential progression rates, biomarker profiles (FDG-PET and CSF Aβ42), and cognitive trajectories: Subtype 1, subcortical-first pattern; Subtype 2, executive–cortical pattern; Subtype 3, disconnection pattern; and Subtype 4, frontal–executive pattern. Stage-dependent changes revealed systematic deterioration across diverse cognitive domains, particularly in learning acquisition, visuospatial processing, and functional abilities. This data-driven approach captures clinically meaningful disease heterogeneity and improves prognostication in MCI, potentially enabling more personalized therapeutic strategies and clinical trial design. 
    more » « less
  2. ; ; ; ; ; ; (, Alzheimers dementia)
    INTRODUCTION: It is unclear whether aggregated plasma protein risk scores (PPRS) could be useful to predict the risks of mild cognitive impairment (MCI) and Alzheimer’s disease (AD). METHODS: The Cox proportional hazard model with the LASSO penalty was used to build the PPRS for MCI and AD in 1,515 Framingham Heart Study Generation2 with 1,128 proteins measured in plasma at exam 5 [cognitive normal (CN)=1,258, MCI=129, AD=128]. RESULTS: MCI PPRS had a hazard ratio (HR) of 6.97[5.34,9.12], with a discriminating power (C-index=82.52%). AD PPRS had an HR of 5.74[4.67,7.05] (C-index=88.15%). Both PPRSs were also significantly associated with cognitive changes, brain-atrophy, and plasma AD biomarkers. Proteins in the MCI and AD PPRSs were enriched in several pathways related to leukocyte, chemotaxis, immunity, inflammation, and cellular migration. DISCUSSION: This study suggests that PPRS serve well to predict the risk of developing MCI and AD as well as cognitive changes and AD related pathogenesis in the brain. 
    more » « less
  3. ; ; ; ; ; ; ; ; ; ; et al (, Alzheimer's & Dementia)
    Abstract INTRODUCTIONAlzheimer's disease (AD) initiates years prior to symptoms, underscoring the importance of early detection. While amyloid accumulation starts early, individuals with substantial amyloid burden may remain cognitively normal, implying that amyloid alone is not sufficient for early risk assessment. METHODSGiven the genetic susceptibility of AD, a multi‐factorial pseudotime approach was proposed to integrate amyloid imaging and genotype data for estimating a risk score. Validation involved association with cognitive decline and survival analysis across risk‐stratified groups, focusing on patients with mild cognitive impairment (MCI). RESULTSOur risk score outperformed amyloid composite standardized uptake value ratio in correlation with cognitive scores. MCI subjects with lower pseudotime risk score showed substantial delayed onset of AD and slower cognitive decline. Moreover, pseudotime risk score demonstrated strong capability in risk stratification within traditionally defined subgroups such as early MCI, apolipoprotein E (APOE) ε4+ MCI,APOEε4– MCI, and amyloid+ MCI. DISCUSSIONOur risk score holds great potential to improve the precision of early risk assessment. HighlightsAccurate early risk assessment is critical for the success of clinical trials.A new risk score was built from integrating amyloid imaging and genetic data.Our risk score demonstrated improved capability in early risk stratification. 
    more » « less
  4. ; ; ; ; ; (, Journal of Alzheimer's Disease)
    Background: Sex differences impact Alzheimer’s disease (AD) neuropathology, but cell-to-network level dysfunctions in the prodromal phase are unclear. Alterations in hippocampal excitation-inhibition balance (EIB) have recently been linked to early AD pathology. Objective: Examine how AD risk factors (age, APOE ɛ4, amyloid-β) relate to hippocampal EIB in cognitively normal males and females using connectome-level measures. Methods: Individuals from the OASIS-3 cohort (age 42–95) were studied (N = 437), with a subset aged 65+ undergoing neuropsychological testing (N = 231). Results: In absence of AD risk factors (APOE ɛ4/Aβ+), whole-brain EIB decreases with age more significantly in males than females (p = 0.021, β= –0.007). Regression modeling including APOE ɛ4 allele carriers (Aβ–) yielded a significant positive AGE-by-APOE interaction in the right hippocampus for females only (p = 0.013, β= 0.014), persisting with inclusion of Aβ+ individuals (p = 0.012, β= 0.014). Partial correlation analyses of neuropsychological testing showed significant associations with EIB in females: positive correlations between right hippocampal EIB with categorical fluency and whole-brain EIB with the Trail Making Test (p < 0.05). Conclusions: Sex differences in EIB emerge during normal aging and progresses differently with AD risk. Results suggest APOE ɛ4 disrupts hippocampal balance more than amyloid in females. Increased excitation correlates positively with neuropsychological performance in the female group, suggesting a duality in terms of potential beneficial effects prior to cognitive impairment. This underscores the translational relevance of APOE ɛ4 related hyperexcitation in females, potentially informing therapeutic targets or early interventions to mitigate AD progression in this vulnerable population. 
    more » « less
  5. ; ; ; ; ; ; ; ; ; ; et al (, Ageing Research Reviews)
    Neuroimaging and biofluid biomarkers provide a proxy of pathological changes for Alzheimer’s disease (AD) and are useful in improving diagnosis and assessing disease progression. However, it is not clear how race/ethnicity and different prevalence of AD risks impact biomarker levels. In this narrative review, we survey studies focusing on comparing biomarker differences between non-Hispanic White American(s) (NHW), African American(s) (AA), Hispanic/Latino American(s) (HLA), and Asian American(s) with normal cognition, mild cognitive impairment, and dementia. We found no strong evidence of racial and ethnic differences in imaging biomarkers after controlling for cognitive status and cardiovascular risks. For biofluid biomarkers, in AA, higher levels of plasma Aβ42/Aβ40, and lower levels of CSF total tau and p-tau 181, were observed after controlling for APOE status and comorbidities compared to NHW. Examining the impact of AD risks and comorbidities on biomarkers and their contributions to racial/ethnic differences in cognitive impairment are critical to interpreting biomarkers, understanding their generalizability, and eliminating racial/ethnic health disparities. 
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email