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Alzheimer’s Disease and Related Disorders: Recent Advances in Prevention, Diagnosis and Therapy

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Clinical Neurology".

Deadline for manuscript submissions: 25 February 2026 | Viewed by 1115

Special Issue Editor

Prof. Dr. Daniel H. S. Silverman

E-Mail Website
Guest Editor
Ahmanson Translational Imaging Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA 90095-7370, USA
Interests: cognition; prodromal; Alzheimer's; Alzheimer; dementia; mild cognitive impairment; mild decline in cognition; disease-modifying; amyloid; tau; neuroinflammation; biomarkers; neuroimaging; PET; PET/CT; PET/MRI

Special Issue Information

Dear Colleagues,

Neurodegenerative disorders leading to cognitive decline are rapidly rising in prevalence in most developed countries, largely because of the increasing median age of their populations. This rise poses potentially major adverse consequences with respect to neurologic and overall health, and caregiver burden. A major thrust of research in this area over the past three decades has been the development and refinement of fluid and neuroimaging biomarkers that can identify these disorders in their earliest stages and guide the implementation of therapies that will be the most effective at the point in time that irreversible neurologic damage is minimal or has not yet occurred. This Special Issue focuses on the latest developments in the biomedical field that promise to contribute to, or have already yielded, significant clinical benefits to people at risk for developing these disorders, or who are already suffering from their debilitating effects.

Prof. Dr. Daniel H. S. Silverman
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cognition
  • prodromal
  • Alzheimer’s
  • Alzheimer
  • dementia
  • mild cognitive impairment
  • mild decline in cognition
  • disease-modifying
  • amyloid
  • tau
  • neuroinflammation
  • biomarkers
  • neuroimaging
  • PET
  • PET/CT
  • PET/MRI

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Published Papers (2 papers)

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28 pages, 1227 KB  
Review
Clinical Significance of APOE4 Genotyping: Potential for Personalized Therapy and Early Diagnosis of Alzheimer’s Disease
by Jelena Rajič Bumber, Valentino Rački, Silvestar Mežnarić, Gordana Pelčić and Jasenka Mršić-Pelčić
J. Clin. Med. 2025, 14(17), 6047; https://doi.org/10.3390/jcm14176047 - 26 Aug 2025
Viewed by 578
Abstract
Apolipoprotein E (APOE) remains the most robust and widely replicated genetic risk factor for late-onset Alzheimer’s disease (AD) susceptibility, with the ε4 allele (APOE4) demonstrating profound associations with accelerated symptom manifestation, enhanced disease trajectory, and modified therapeutic responsiveness. This comprehensive review [...] Read more.
Apolipoprotein E (APOE) remains the most robust and widely replicated genetic risk factor for late-onset Alzheimer’s disease (AD) susceptibility, with the ε4 allele (APOE4) demonstrating profound associations with accelerated symptom manifestation, enhanced disease trajectory, and modified therapeutic responsiveness. This comprehensive review synthesizes contemporary evidence regarding the clinical utility of APOE4 genotyping, emphasizing its integration into personalized therapeutic frameworks and early diagnostic paradigms. The APOE4 variant exerts pathogenic influence through impaired amyloid-β clearance, enhanced tau pathology, and compromised neuronal repair mechanisms that alter disease phenotype. We systematically examine available genotyping methodologies, encompassing polymerase chain reaction (PCR) and next-generation sequencing (NGS) platforms, and evaluate their practical implementation within clinical environments. Recent investigations demonstrate that APOE4 status profoundly influences therapeutic efficacy, particularly with anti-amyloid interventions such as lecanemab, where carriers exhibit enhanced treatment response alongside increased adverse event susceptibility. Emerging gene therapeutic approaches show promise in mitigating APOE4-associated risks through targeted molecular interventions. The integration of APOE4 genotyping with fluid biomarkers and neuroimaging techniques enables refined patient stratification and enhanced diagnostic precision, facilitating earlier intervention windows that optimize therapeutic outcomes before irreversible neuronal damage occurs. This review underscores APOE4 testing as a transformative component of precision medicine in AD management, emphasizing its contribution to diagnostic refinement, clinical decision support, and targeted therapeutic interventions. Full article
(This article belongs to the Special Issue Alzheimer’s Disease and Related Disorders: Recent Advances in Prevention, Diagnosis and Therapy)
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10 pages, 1282 KB  
Brief Report
Novel Association of the Presenilin-1 (Leu282Arg) Mutation with Isolated Spastic Paraparesis: Case Presentation and Review of Current Evidence
by María De la Sen-Domínguez, Manuel Delgado-Alvarado, Marta Torres-Barquin, Remedios Quirce and Javier Riancho
J. Clin. Med. 2025, 14(17), 6150; https://doi.org/10.3390/jcm14176150 - 30 Aug 2025
Viewed by 394
Abstract
Background: Although Presenilin-1 (PSEN1) mutations are classically associated with early-onset Alzheimer’s disease (AD), spastic paraparesis (SP) may occasionally represent as an initial or even isolated clinical manifestation. Methods: We report the novel association of a PSEN1 mutation (Leu282Arg) with isolated SP [...] Read more.
Background: Although Presenilin-1 (PSEN1) mutations are classically associated with early-onset Alzheimer’s disease (AD), spastic paraparesis (SP) may occasionally represent as an initial or even isolated clinical manifestation. Methods: We report the novel association of a PSEN1 mutation (Leu282Arg) with isolated SP at onset in a patient with a family history of early-onset AD. Additionally, we reviewed previously published cases describing similar presentations related to PSEN1 mutations. Results: The age of reported patients ranged from 24 to 60 years. The most common clinical course included the presence of cotton wool plaques and a progressive development of cognitive decline following the onset of SP. A positive family history of either motor or cognitive symptoms was consistently observed. Conclusions: Our findings emphasize the clinical importance of considering PSEN1 mutations in the differential diagnosis of patients presenting with spastic paraparesis, particularly in the presence of cognitive symptoms, cerebral amyloid angiopathy, or a family history of AD. Full article
(This article belongs to the Special Issue Alzheimer’s Disease and Related Disorders: Recent Advances in Prevention, Diagnosis and Therapy)
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