MaltSci 麦伴科研

Appearance

Curated Papers > Highly Cited Authoritative Literature on "Alzheimer's Disease"

Heavy Metals Exposure and Alzheimer's Disease and Related Dementias. ​

Literature Information ​

DOI10.3233/JAD-200282
PMID32651318
JournalJournal of Alzheimer's disease : JAD
Impact Factor3.1
JCR QuartileQ2
Publication Year2020
Times Cited114
KeywordsCadmium, epidemiology, heavy metal, lead, manganese
Literature TypeJournal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review
ISSN1387-2877
Pages1215-1242
Issue76(4)
AuthorsKelly M Bakulski, Young Ah Seo, Ruby C Hickman, Daniel Brandt, Harita S Vadari, Howard Hu, Sung Kyun Park

TL;DR ​

This study reviews the associations between heavy metals—lead, cadmium, and manganese—and the risk of Alzheimer's disease and related dementias, highlighting that these neurotoxicants can negatively impact cognitive function and may contribute to the disease pathology. It emphasizes the need for longitudinal epidemiological studies to better understand the extent of these environmental exposures on Alzheimer's risk, as even minor increases in risk could significantly affect public health given the widespread prevalence of these metals.

Search for more papers on MaltSci.com ​

Cadmium · epidemiology · heavy metal · lead · manganese

Abstract ​

Alzheimer's disease and related dementias lack effective treatment or cures and are major public health challenges. Risk for Alzheimer's disease and related dementias is partially attributable to environmental factors. The heavy metals lead, cadmium, and manganese are widespread and persistent in our environments. Once persons are exposed to these metals, they are adept at entering cells and reaching the brain. Lead and cadmium are associated with numerous health outcomes even at low levels of exposure. Although manganese is an essential metal, deficiency or environmental exposure or high levels of the metal can be toxic. In cell and animal model systems, lead, cadmium, and manganese are well documented neurotoxicants that contribute to canonical Alzheimer's disease pathologies. Adult human epidemiologic studies have consistently shown lead, cadmium, and manganese are associated with impaired cognitive function and cognitive decline. No longitudinal human epidemiology study has assessed lead or manganese exposure on Alzheimer's disease specifically though two studies have reported a link between cadmium and Alzheimer's disease mortality. More longitudinal epidemiologic studies with high-quality time course exposure data and incident cases of Alzheimer's disease and related dementias are warranted to confirm and estimate the proportion of risk attributable to these exposures. Given the widespread and global exposure to lead, cadmium, and manganese, even small increases in the risks of Alzheimer's disease and related dementias would have a major population impact on the burden on disease. This article reviews the experimental and epidemiologic literature of the associations between lead, cadmium, and manganese on Alzheimer's disease and related dementias and makes recommendations of critical areas of future investment.

MaltSci.com AI Research Service ​

Intelligent ReadingAnswer any question about the paper and explain complex charts and formulas
Locate StatementsFind traces of a specific claim within the paper
Add to KBasePerform data extraction, report drafting, and advanced knowledge mining

Primary Questions Addressed ​

  1. What are the specific mechanisms by which heavy metals like lead, cadmium, and manganese contribute to the pathophysiology of Alzheimer's disease?
  2. How do the levels of exposure to heavy metals correlate with the onset and progression of Alzheimer's disease in different populations?
  3. Are there any potential protective factors or interventions that could mitigate the neurotoxic effects of heavy metals on cognitive function?
  4. How does the timing and duration of heavy metal exposure influence the risk of developing Alzheimer's disease and related dementias?
  5. What role do genetic factors play in an individual's susceptibility to the neurotoxic effects of heavy metals in relation to Alzheimer's disease?

Key Findings ​

Research Background and Objectives ​

Alzheimer's disease and related dementias (ADRD) pose significant public health challenges due to the lack of effective treatments or cures. Environmental factors, particularly exposure to heavy metals such as lead, cadmium, and manganese, are partially responsible for the risk of developing ADRD. This study aims to review the associations between these metals and ADRD, emphasizing the need for longitudinal epidemiological studies to better understand their impact.

Main Methods/Materials/Experimental Design ​

The study employs a comprehensive review methodology, synthesizing existing experimental and epidemiological literature regarding the neurotoxic effects of lead, cadmium, and manganese on cognitive function and ADRD.

Methodological Flowchart ​

Mermaid diagram

Key Results and Findings ​

  • Neurotoxic Effects: Lead and cadmium have been shown to contribute to various health issues, even at low exposure levels, while manganese can be toxic at high levels despite being essential.
  • Cognitive Decline: Epidemiological studies consistently indicate a correlation between exposure to these metals and cognitive decline in adults.
  • Longitudinal Studies: No longitudinal studies specifically examining lead or manganese exposure in relation to ADRD have been conducted, though some studies have linked cadmium exposure to increased mortality from ADRD.

Main Conclusions/Significance/Innovation ​

The review highlights the urgent need for longitudinal studies to quantify the risk of ADRD attributable to lead, cadmium, and manganese exposure. Given the global prevalence of these metals, even minor increases in risk could significantly affect public health and the burden of ADRD. The study calls for targeted research investments in this area to enhance understanding and prevention strategies.

Research Limitations and Future Directions ​

  • Limitations: The review is limited by the lack of longitudinal studies specifically focused on lead and manganese exposure in relation to ADRD. Additionally, the variability in study designs and exposure assessment methods across existing literature complicates direct comparisons.
  • Future Directions: Future research should focus on:
    • Conducting high-quality longitudinal studies to assess the impact of these metals on ADRD incidence.
    • Developing standardized exposure assessment methodologies.
    • Investigating the biological mechanisms through which these metals influence neurodegeneration.
AspectDetails
Metals ExaminedLead, Cadmium, Manganese
Health OutcomesImpaired cognitive function, cognitive decline, ADRD mortality
Research GapsLack of longitudinal studies on lead and manganese
Recommended ActionsInvest in epidemiological studies and mechanism exploration

References ​

  1. Ferroportin is a manganese-responsive protein that decreases manganese cytotoxicity and accumulation. - Zhaobao Yin;Haiyan Jiang;Eun-Sook Y Lee;Mingwei Ni;Keith M Erikson;Dejan Milatovic;Aaron B Bowman;Michael Aschner - Journal of neurochemistry (2010)
  2. Toxicology of choroid plexus: special reference to metal-induced neurotoxicities. - W Zheng - Microscopy research and technique (2001)
  3. Manganese Toxicity Upon Overexposure: a Decade in Review. - Stefanie L O'Neal;Wei Zheng - Current environmental health reports (2015)
  4. Neurotoxic effects and biomarkers of lead exposure: a review. - Talia Sanders;Yiming Liu;Virginia Buchner;Paul B Tchounwou - Reviews on environmental health (2009)
  5. The effects of early life Pb exposure on the expression of IL1-β, TNF-α and Aβ in cerebral cortex of mouse pups. - Ning Li;FangLi Liu;LianJun Song;PingAn Zhang;MingWu Qiao;QiuYan Zhao;WenJie Li - Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) (2014)
  6. Cadmium concentration in blood in an elderly urban population. - M Nordberg;B Winblad;H Basun - Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine (2000)
  7. Lead toxicity update. A brief review. - Nikolas C Papanikolaou;Eleftheria G Hatzidaki;Stamatis Belivanis;George N Tzanakakis;Aristidis M Tsatsakis - Medical science monitor : international medical journal of experimental and clinical research (2005)
  8. Celastrol Attenuates Cadmium-Induced Neuronal Apoptosis via Inhibiting Ca2+ -CaMKII-Dependent Akt/mTOR Pathway. - Ruijie Zhang;Yu Zhu;Xiaoqing Dong;Beibei Liu;Nana Zhang;Xiaoxue Wang;Lei Liu;Chong Xu;Shile Huang;Long Chen - Journal of cellular physiology (2017)
  9. Lewy bodies in Alzheimer's disease: a neuropathological review of 145 cases using alpha-synuclein immunohistochemistry. - R L Hamilton - Brain pathology (Zurich, Switzerland) (2000)
  10. Manganese neurotoxicity, a continuum of dysfunction: results from a community based study. - D Mergler;M Baldwin;S Bélanger;F Larribe;A Beuter;R Bowler;M Panisset;R Edwards;A de Geoffroy;M P Sassine;K Hudnell - Neurotoxicology (1999)

Literatures Citing This Work ​

  1. Cellular and Molecular Mechanisms of Environmental Pollutants on Hematopoiesis. - Pablo Scharf;Milena Fronza Broering;Gustavo Henrique Oliveira da Rocha;Sandra Helena Poliselli Farsky - International journal of molecular sciences (2020)
  2. Aluminium Binding to Modified Amyloid-β Peptides: Implications for Alzheimer's Disease. - Cosmin Stefan Mocanu;Monica Jureschi;Gabi Drochioiu - Molecules (Basel, Switzerland) (2020)
  3. (Ascorb)ing Pb Neurotoxicity in the Developing Brain. - Faraz Ahmad;Ping Liu - Antioxidants (Basel, Switzerland) (2020)
  4. Cognitive Impairment Induced by Lead Exposure during Lifespan: Mechanisms of Lead Neurotoxicity. - Daniela Ramírez Ortega;Dinora F González Esquivel;Tonali Blanco Ayala;Benjamín Pineda;Saul Gómez Manzo;Jaime Marcial Quino;Paul Carrillo Mora;Verónica Pérez de la Cruz - Toxics (2021)
  5. Direct and Indirect Neurotoxic Potential of Metal/Metalloids in Plants and Fungi Used for Food, Dietary Supplements, and Herbal Medicine. - Peter S Spencer;Valerie S Palmer - Toxics (2021)
  6. The Potential Roles of Blood-Brain Barrier and Blood-Cerebrospinal Fluid Barrier in Maintaining Brain Manganese Homeostasis. - Shannon Morgan McCabe;Ningning Zhao - Nutrients (2021)
  7. Bioaccumulation of Toxic Metals in Children Exposed to Urban Pollution and to Cement Plant Emissions. - Agostino Di Ciaula - Exposure and health (2021)
  8. Thiourea Derivatives, Simple in Structure but Efficient Enzyme Inhibitors and Mercury Sensors. - Faizan Ur Rahman;Maryam Bibi;Ezzat Khan;Abdul Bari Shah;Mian Muhammad;Muhammad Nawaz Tahir;Adnan Shahzad;Farhat Ullah;Muhammad Zahoor;Salman Alamery;Gaber El-Saber Batiha - Molecules (Basel, Switzerland) (2021)
  9. Impact of environmental toxicants on p38- and ERK-MAPK signaling pathways in the central nervous system. - Omamuyovwi M Ijomone;Joy D Iroegbu;Michael Aschner;Julia Bornhorst - Neurotoxicology (2021)
  10. Exposure to Environmental Arsenic and Emerging Risk of Alzheimer's Disease: Perspective Mechanisms, Management Strategy, and Future Directions. - Md Ataur Rahman;Md Abdul Hannan;Md Jamal Uddin;Md Saidur Rahman;Md Mamunur Rashid;Bonglee Kim - Toxics (2021)

... (104 more literatures)

© 2025 MaltSci - We reshape scientific research with AI technology