Top Research Papers on Alzheimer's Disease

The authors of this Perspective suggest that Alzheimer disease’s lack of a singular common pathogenesis prevents it from being regarded as a straightforward ‘disease’ and that treatment will therefore require a multifaceted approach.

In this Seminar, we highlight the main developments in the field of Alzheimer's disease. The most recent data indicate that, by 2050, the prevalence of dementia will double in Europe and triple worldwide, and that estimate is 3 times higher when based on a biological (rather than clinical) definition of Alzheimer's disease. The earliest phase of Alzheimer's disease (cellular phase) happens in parallel with accumulating amyloid β, inducing the spread of tau pathology. The risk of Alzheimer's disease is 60-80% dependent on heritable factors, with more than 40 Alzheimer's disease-associated genet...

This Primer conceives of AD biology as the brain disorder that results from a complex interplay of loss of synaptic homeostasis and dysfunction in the highly interrelated endosomal/lysosomal clearance pathways in which the precursors, aggregated species and post-translationally modified products of Aβ and tau play important roles.

Major strides in biomarker-based diagnosis of AD and recent advances in targeted therapeutic approaches may have shifted the perspective but also highlight the continuous importance of postmortem analysis of the brain in neurodegenerative diseases.

The authors explore the impact of extrinsic factors, such as brain trauma, diet and infections, and host-intrinsic factors, such as the activity of microglial cells and other immune, vascular and neuronal cell populations, on disease development and highlight emerging drugs that target this inflammatory component of Alzheimer disease.

A wide range of comorbid diseases is associated with Alzheimer's disease (AD), the most common neurodegenerative disease worldwide. Evidence from clinical and molecular studies suggest that chronic diseases, including diabetes, cardiovascular disease, depression, and inflammatory bowel disease, may be associated with an increased risk of AD in different populations. Disruption in several shared biological pathways has been proposed as the underlying mechanism for the association between AD and these comorbidities. Notably, inflammation is a common dysregulated pathway shared by most of the com...

The intent of this paper was to review the existing literature and determine, using the Bradford Hill criteria, whether periodontal disease is causally related to Alzheimer's disease.

The properties of the key proteins comprising the amyloid plaques and neurofibrillary tangles that define the neuropathology of AD have been identified and combined with extensive genetic studies, a sequence of lesion formation in brain networks serving memory and cognition is suggested.

A model is proposed that determines individuals' belonging to one of the AD subtypes based on the combination of protective factors, risk factors, and concomitant non-AD brain pathologies, and can be used along the A/T/N classification scheme for AD biomarkers.

The mechanisms through which synapses degenerate in the AD brain are highlighted, and the ways in which understanding of the mechanisms of synaptic degeneration is leading to new therapeutic approaches for AD are covered.

This study shows that PUTG component scores were significantly associated with diagnostic group and AD biomarkers, a finding that was more pronounced in APOE ε4 carriers.

In the future, additional consideration of sex- and ethnicity-specific contributions to risk as well as the contribution of complex gene-gene and gene-environment interactions will likely be necessary to further improve the understanding of AD genetic architecture.

The association of APOE with AD, the APOE isoform specific effects within brain and periphery, and potential therapeutics are reviewed.

It is demonstrated that astrocyte biomarkers are consistently altered in AD and supports further investigation for their inclusion in the AD clinical research framework for observational and interventional studies.

Several potential pathological pathways of vascular involvement in AD are discussed including dysregulation of neurovascular coupling, disruption of the blood brain barrier, and reduced clearance of metabolite waste such as beta-amyloid, a toxic peptide considered the hallmark of AD.

The Alzheimer's Disease Neuroimaging Initiative (ADNI) has accumulated 15 years of clinical, neuroimaging, cognitive, biofluid biomarker and genetic data, andBiofluid samples available to researchers, resulting in more than 3500 publications.

The current review focuses on the state of literature on molecular and metabolic pathways modulating the heart–brain axis underlying the potential association of midlife CVD risk factors and their effect on AD and related dementias.

An integrated biological and clinical staging scheme is described that accommodates the fact that common copathologies, cognitive reserve, and resistance may modify relationships between clinical and biological AD stages.

Additional data are needed before use of BBMs as stand‐alone diagnostic AD markers, or before considering use in primary care, and it is recommended to cautiously start using BBMs in specialized memory clinics as part of the diagnostic work‐up of patients with cognitive symptoms.

Abstract This article describes the public health impact of Alzheimer's disease (AD), including prevalence and incidence, mortality and morbidity, use and costs of care, and the ramifications of AD for family caregivers, the dementia workforce, and society. The Special Report discusses Americans’ attitudes about early diagnosis and treatment of AD. An estimated 7.2 million Americans age 65 and older live with Alzheimer's dementia today. This number could grow to 13.8 million by 2060, barring the development of medical breakthroughs to prevent or cure AD. Official AD death certificates recorded...

This article describes the public health impact of Alzheimer's disease (AD), including prevalence and incidence, mortality and morbidity, use and costs of care and the ramifications of AD for family caregivers, the dementia workforce and society. The Special Report discusses the larger health care system for older adults with cognitive issues, focusing on the role of caregivers and non-physician health care professionals. An estimated 6.9 million Americans age 65 and older are living with Alzheimer's dementia today. This number could grow to 13.8 million by 2060, barring the development of med...

The public health impact of Alzheimer's disease (AD), including incidence and prevalence, mortality and morbidity, use and costs of care, and the overall impact on family caregivers, the dementia workforce and society are described are described.

Abstract In the last 20 years, research focused on developing retinal imaging as a source of potential biomarkers for Alzheimer's disease and other neurodegenerative diseases, has increased significantly. The Alzheimer's Association and the Alzheimer's & Dementia: Diagnosis, Assessment, Disease Monitoring editorial team (companion journal to Alzheimer's & Dementia ) convened an interdisciplinary discussion in 2019 to identify a path to expedite the development of retinal biomarkers capable of identifying biological changes associated with AD, and for tracking progression of disease sev...

The pathophysiology of AD is reviewed and the application prospects of related stem cells based on cell type are reviewed, including human embryonic stem cells or induced pluripotent stem cell–derived neural cells.

The potential disease-modifying agents tested in clinical trials are discussed, the information of drugs that are still under clinical evaluation is updated and updated and the tau-targeting therapies are discussed.

Presented is a review of all previously failed Alzheimer's disease clinical trials and the rationale for their failures.

After many years from the introduction in therapy of ChE-Is, the combination with other classes of drugs may represent the chance for a renewed interest of Ch E-Is in the treatment of adult-onset dementia disorders.

This Review provides a comprehensive update on the current knowledge of the genetics of APOE and its role in Alzheimer and other neurodegenerative diseases, and summarizes emerging APOE-targeted therapies designed to prevent or slow down Alzheimer disease.

This Review highlights promising compounds to prioritize for clinical trials in individuals with AD, and discusses the value of Delphi consensus methodology and evidence-based reviews to inform this prioritization process.

A comprehensive targeted review of the PubMed-indexed literature to examine the humanistic and economic burden of AD (including MCI) in North America, Europe, and Asia and identified a range of factors associated with quality of life (QoL): some factors were positively associated with QoL, including caregiver relationship, religiosity, social engagement, and ability to engage in activities of daily living (ADL), whereas other factors were associated with poorer Qos.

This review focuses on recent findings on EC dysfunction in AD, and discusses the potential pathways for mitigating AD progression by protecting the EC.

Recent advancements in the understanding of innate immunity and inflammation in AD onset and progression are highlighted and it is suggested that many of these AD risk factors influence AD progression via modulation of microglia and immune responses.

The public health impact of Alzheimer's disease (AD), including incidence and prevalence, mortality and morbidity, use and costs of care, and the overall impact on caregivers and society is described, is described.

This review will outline the growing molecular and clinical evidence implicating ferroptosis in the pathogenesis of AD, with implications for disease‐modifying therapies.

The shift in clinical trials away from therapies targeting neurotransmitter systems that provide symptomatic relief, and towards anti‐aggregation, anti-inflammatory, anti‐oxidant, and regeneration strategies that aim to inhibit the root causes of disease progression is revealed.

This randomized, double-blind, placebo-controlled, 18-month phase 3 trial enrolled 1736 participants with early symptomatic Alzheimer disease (mild cognitive impairment/mild dementia) with amyloid and low/medium or high tau pathology based on positron emission tomography imaging from June 2020 to November 2021 to assess efficacy and adverse events of donanemab.

The future challenges of meeting care demands for the growing number of people living with Alzheimer's dementia in the United States with a particular emphasis on primary care are discussed, including recommendations for maximizing quality care in the face of the shortage of specialists and training challenges in primary care.

This article describes the public health impact of Alzheimer's disease, including prevalence and incidence, mortality and morbidity, use and costs of care, and the overall impact on family caregivers, the dementia workforce and society. The Special Report examines the patient journey from awareness of cognitive changes to potential treatment with drugs that change the underlying biology of Alzheimer's. An estimated 6.7 million Americans age 65 and older are living with Alzheimer's dementia today. This number could grow to 13.8 million by 2060 barring the development of medical breakthroughs to...

Recent results that enable pathological staging of AD with neuroimaging and fluid-based biomarkers are reviewed, with a particular emphasis on the role of amyloid, tau and neuroinflammation in disease pathogenesis.

Recent Aβ-immunotherapy trials have yielded the first clear evidence that removing aggregated Aβ from the brains of symptomatic patients can slow the progression of Alzheimer's disease. The clinical benefit achieved in these trials has been modest, however, highlighting the need for both a deeper understanding of disease mechanisms and the importance of intervening early in the pathogenic cascade. An immunoprevention strategy for Alzheimer's disease is required that will integrate the findings from clinical trials with mechanistic insights from preclinical disease models to select promising an...