Appearance
Alzheimer's disease.
Literature Information
| DOI | 10.1111/ene.13439 |
|---|---|
| PMID | 28872215 |
| Journal | European journal of neurology |
| Impact Factor | 3.9 |
| JCR Quartile | Q1 |
| Publication Year | 2018 |
| Times Cited | 1142 |
| Keywords | Alzheimer's disease, epidemiology, genetics, pathogenesis, pathology |
| Literature Type | Journal Article, Research Support, Non-U.S. Gov't, Review |
| ISSN | 1351-5101 |
| Pages | 59-70 |
| Issue | 25(1) |
| Authors | C A Lane, J Hardy, J M Schott |
TL;DR
This review examines the epidemiology, genetics, and pathogenesis of Alzheimer's disease, highlighting the significance of its protracted preclinical phase in informing new therapeutic strategies. The findings underscore the potential shift from treatment-focused approaches to prevention, addressing the growing global health challenge posed by this common cause of dementia.
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Alzheimer's disease · epidemiology · genetics · pathogenesis · pathology
Abstract
Alzheimer's disease, the commonest cause of dementia, is a growing global health concern with huge implications for individuals and society. In this review, current understanding of the epidemiology, genetics, pathology and pathogenesis of Alzheimer's disease is outlined, before its clinical presentation and current treatment strategies are discussed. Finally, the review discusses how our enhanced understanding of Alzheimer pathogenesis, including the recognition of a protracted preclinical phase, is informing new therapeutic strategies with the aim of moving from treatment to prevention.
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Primary Questions Addressed
- What are the latest findings on the interaction between lifestyle factors and Alzheimer's disease progression?
- How do emerging biomarkers like amyloid β oligomers and synaptic markers compare to traditional biomarkers in terms of diagnostic accuracy?
- What role does tau PET imaging play in the early diagnosis and differentiation of Alzheimer's disease from other types of dementia?
- How might the concept of preclinical Alzheimer's disease change the approach to early intervention and treatment strategies?
- What are the implications of combining anti-Alzheimer's therapies with lifestyle interventions for long-term patient outcomes?
Key Findings
Research Background and Purpose
Alzheimer’s disease (AD) is the most common cause of dementia, posing a significant global health challenge. This review aims to summarize the current understanding of AD's epidemiology, genetics, pathology, and pathogenesis, while discussing clinical presentations and treatment strategies. It emphasizes the importance of recognizing a protracted preclinical phase of AD to inform new therapeutic strategies aimed at prevention rather than just treatment.
Main Methods/Materials/Experimental Design
The review synthesizes findings from various studies on AD, including epidemiological data, genetic associations, and insights from neuroimaging and pathological studies. The following flowchart illustrates the key areas explored in the review:
Key Results and Findings
- Epidemiology: Approximately 44 million people currently live with dementia, projected to triple by 2050. AD accounts for 50-75% of dementia cases, with a significant prevalence increase after age 65.
- Genetics: Sporadic AD is influenced by genetic factors, with the APOE ε4 allele being the most significant risk factor. Over 20 genetic risk factors have been identified through genome-wide association studies (GWAS).
- Pathology: Characteristic features of AD include amyloid plaques and neurofibrillary tangles (NFTs). The progression of amyloid deposition and tau pathology is critical to understanding disease development.
- Pathogenesis: The amyloid hypothesis suggests that the accumulation of β-amyloid is central to AD pathology, leading to neurodegeneration. Recent evidence indicates that soluble Aβ oligomers may be more toxic than fibrillar amyloid.
- Clinical Features: The disease typically presents with progressive memory loss, eventually affecting daily living activities. Atypical presentations include posterior cortical atrophy and logopenic aphasia.
- Diagnostic Criteria: New criteria recognize preclinical stages of AD, allowing for earlier and more accurate diagnosis using biomarkers.
- Treatment: Currently, there are no disease-modifying treatments. Symptomatic treatments include acetylcholinesterase inhibitors and memantine, with limited efficacy.
Main Conclusions/Significance/Innovation
The review highlights the complexity of AD and the interplay of genetic, environmental, and pathological factors. The recognition of a preclinical phase offers new avenues for intervention, emphasizing the need for early diagnosis and potential preventive strategies. Future research is directed towards identifying effective disease-modifying therapies and understanding the role of neuroinflammation in AD progression.
Research Limitations and Future Directions
- Limitations: The review primarily synthesizes existing literature without presenting new experimental data. There is a need for longitudinal studies to better understand the progression from preclinical to clinical stages of AD.
- Future Directions: Ongoing clinical trials are investigating new therapies targeting amyloid and tau pathologies. The development of personalized medicine approaches based on genetic risk profiles and biomarker data is a promising avenue for future research. Additionally, understanding the role of lifestyle factors in AD prevention remains crucial.
| Section | Key Points |
|---|---|
| Epidemiology | 44 million currently affected; projected to triple by 2050. AD is the leading cause of dementia. |
| Genetics | APOE ε4 is the major risk factor; over 20 genetic risk factors identified. |
| Pathology | Characterized by amyloid plaques and NFTs; mixed pathologies common. |
| Pathogenesis | Amyloid hypothesis central; soluble oligomers may be more toxic than plaques. |
| Clinical Features | Memory loss is typical; atypical presentations noted. |
| Diagnostic Criteria | New criteria incorporate preclinical stages; biomarkers enhance diagnosis. |
| Treatment | No disease-modifying treatments; symptomatic treatments have limited efficacy. |
This structured summary captures the essence of the review on Alzheimer’s disease, reflecting the complexity and urgency of addressing this growing health concern.
Literatures Citing This Work
- Gasotransmitter hydrogen sulfide signaling in neuronal health and disease. - Bindu D Paul;Solomon H Snyder - Biochemical pharmacology (2018)
- Application of Metabolomics in Alzheimer's Disease. - Jordan Maximillian Wilkins;Eugenia Trushina - Frontiers in neurology (2017)
- A Systematic Review of Antiamyloidogenic and Metal-Chelating Peptoids: Two Structural Motifs for the Treatment of Alzheimer's Disease. - Sherri C Young - Molecules (Basel, Switzerland) (2018)
- ABCA7 and Pathogenic Pathways of Alzheimer's Disease. - Tomonori Aikawa;Marie-Louise Holm;Takahisa Kanekiyo - Brain sciences (2018)
- Genetic Variation in Genes Underlying Diverse Dementias May Explain a Small Proportion of Cases in the Alzheimer's Disease Sequencing Project. - Elizabeth E Blue;Joshua C Bis;Michael O Dorschner;Debby W Tsuang;Sandra M Barral;Gary Beecham;Jennifer E Below;William S Bush;Mariusz Butkiewicz;Carlos Cruchaga;Anita DeStefano;Lindsay A Farrer;Alison Goate;Jonathan Haines;Jim Jaworski;Gyungah Jun;Brian Kunkle;Amanda Kuzma;Jenny J Lee;Kathryn L Lunetta;Yiyi Ma;Eden Martin;Adam Naj;Alejandro Q Nato;Patrick Navas;Hiep Nguyen;Christiane Reitz;Dolly Reyes;William Salerno;Gerard D Schellenberg;Sudha Seshadri;Harkirat Sohi;Timothy A Thornton;Otto Valadares;Cornelia van Duijn;Badri N Vardarajan;Li-San Wang;Eric Boerwinkle;Josée Dupuis;Margaret A Pericak-Vance;Richard Mayeux;Ellen M Wijsman; - Dementia and geriatric cognitive disorders (2018)
- Cysteine Metabolism in Neuronal Redox Homeostasis. - Bindu D Paul;Juan I Sbodio;Solomon H Snyder - Trends in pharmacological sciences (2018)
- Pathologically Confirmed Alzheimer's Disease in APOE ɛ2 Homozygotes is Rare but Does Occur. - Faissal Stipho;Robert Jackson;Marwan N Sabbagh - Journal of Alzheimer's disease : JAD (2018)
- Development of Azeliragon, an Oral Small Molecule Antagonist of the Receptor for Advanced Glycation Endproducts, for the Potential Slowing of Loss of Cognition in Mild Alzheimer's Disease. - A H Burstein;M Sabbagh;R Andrews;C Valcarce;I Dunn;L Altstiel - The journal of prevention of Alzheimer's disease (2018)
- Bacteroidetes Neurotoxins and Inflammatory Neurodegeneration. - Yuhai Zhao;Walter J Lukiw - Molecular neurobiology (2018)
- The Role of Immunosenescence in Neurodegenerative Diseases. - Erica Costantini;Chiara D'Angelo;Marcella Reale - Mediators of inflammation (2018)
... (1132 more literatures)
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