【AI Explained】Prevalence of Alzheimer''s disease pathology in the community.

Literature Information

TL;DR

This study assessed the prevalence of Alzheimer’s disease neuropathological changes (ADNCs) using phosphorylated tau in plasma samples from a Norwegian cohort aged over 57, revealing that ADNCs significantly increase with age, reaching 65.2% in individuals over 90. The findings indicate a higher prevalence of Alzheimer’s disease dementia in older adults and suggest a need to reevaluate the prevalence of preclinical Alzheimer’s disease in younger populations.

Search for more papers on MaltSci.com

Alzheimer’s disease · neuropathological changes · blood-based biomarkers · cognitive impairment · epidemiology

Abstract

The prevalence of Alzheimer’s disease neuropathological changes (ADNCs), the leading cause of cognitive impairment, remains uncertain. Recent blood-based biomarkers enable scalable assessment of ADNCs1. Here we measured phosphorylated tau at threonine 217 in 11,486 plasma samples from a Norwegian population-based cohort of individuals over 57 years of age as a surrogate marker for ADNCs. The estimated prevalence of ADNCs increased with age, from less than 8% in people 58-69.9 years of age to 65.2% in those over 90 years of age. Among participants aged 70 years or older, 10% had preclinical Alzheimer’s disease, 10.4% had prodromal Alzheimer’s disease and 9.8% had Alzheimer’s disease dementia. Furthermore, among those 70 years of age or older, ADNCs were present in 60% of people with dementia, in 32.6% of those with mild cognitive impairment and in 23.5% of the cognitively unimpaired group. Our findings suggest a higher prevalence of Alzheimer’s disease dementia in older individuals and a lower prevalence of preclinical Alzheimer’s disease in younger groups than previously estimated2.

MaltSci.com AI Research Service

Primary Questions Addressed

1. What are the implications of the increasing prevalence of Alzheimer’s disease neuropathological changes with age for public health policies?
2. How do blood-based biomarkers like phosphorylated tau at threonine 217 compare to traditional diagnostic methods for Alzheimer’s disease?
3. What factors might contribute to the observed differences in prevalence rates of preclinical and prodromal Alzheimer’s disease among various age groups?
4. How can community-based interventions be designed to address the growing prevalence of Alzheimer’s disease dementia in older populations?
5. What role does genetic predisposition play in the development of Alzheimer’s disease neuropathological changes in different demographic groups?

Key Findings

Research Summary

Background and Objectives

Alzheimer’s disease (AD) is the leading cause of cognitive impairment, and its neuropathological changes (ADNCs) remain uncertain in prevalence within the general population. This study aimed to measure the prevalence of ADNCs in a community setting using plasma phosphorylated tau at threonine 217 (pTau217) as a surrogate marker. The objectives were to assess the prevalence of ADNCs across age and sex groups, explore associations with demographic and cognitive factors, and determine the eligibility for disease-modifying therapies (DMTs) among older adults.

Main Methods/Materials/Experimental Design

This study utilized a nested cross-sectional design within the Trøndelag Health (HUNT) study, focusing on individuals aged 58 years and older. The study included 11,486 plasma samples, with 2,537 participants from HUNT3 (ages 58–69.9) and 8,949 from HUNT4 (ages 70+). The presence of ADNCs was determined by measuring plasma pTau217 levels using a validated commercial kit.

Key Components of the Study Design:

• Study Design: Nested cross-sectional study within a population-based cohort.
• Recruitment Criteria: Participants aged 58 years and older, with cognitive assessments performed for those 70 and older.
• Intervention: Measurement of plasma pTau217 concentrations to assess ADNCs.
• Endpoints: Primary endpoint was the prevalence of ADNCs; secondary endpoints included cognitive diagnosis and eligibility for DMTs.
• Statistical Analysis: Utilized weighted estimates to adjust for selection bias and assessed associations using logistic regression.

Key Results and Findings

The study found that the prevalence of ADNCs increased significantly with age:

• Less than 8% in individuals aged 58–69.9 years.
• 65.2% in individuals aged over 90 years. Among participants aged 70 years or older:
• 10% had preclinical AD.
• 10.4% had prodromal AD.
• 9.8% had AD dementia. ADNCs were present in 60% of those with dementia, 32.6% of those with mild cognitive impairment (MCI), and 23.5% of cognitively unimpaired individuals.

Additional findings included:

• Higher prevalence of ADNCs among individuals with lower education levels and those carrying one or two APOE ε4 alleles.
• An inverse association between estimated glomerular filtration rate (eGFR) and plasma pTau217 concentrations.

Conclusions/Significance/Innovation

The study provides new insights into the prevalence of ADNCs in a large, community-based cohort, indicating higher rates of AD dementia among older individuals than previously reported. The use of blood-based biomarkers like pTau217 facilitates large-scale studies, which are crucial for understanding the public health implications of AD. The findings suggest a need for updated prevalence estimates that could influence future healthcare planning and treatment eligibility for DMTs.

Limitations and Future Directions

The study acknowledges several limitations:

• The reliance on self-reported medical histories may lead to inaccuracies.
• The cohort is predominantly white, limiting generalizability to more diverse populations.
• Cross-sectional design may not capture the full spectrum of ADNC development over time.

Future research should focus on longitudinal studies to track changes in ADNC prevalence, explore the impact of lifestyle factors on AD pathology, and validate findings in more ethnically diverse populations. Further investigation into the clinical implications of intermediate pTau217 results is also warranted.

References

1. Detection of Alzheimer Neuropathology in Alzheimer and Non-Alzheimer Clinical Syndromes With Blood-Based Biomarkers. - Lawren VandeVrede;Hanna Cho;Mark Sanderson-Cimino;Fattin Wekselman;Yann Cobigo;Maria Luisa Gorno-Tempini;Hilary W Heuer;Joel H Kramer;Argentina Lario Lago;Dana Leichter;Peter Ljubenkov;Bruce L Miller;David C Perry;Gil D Rabinovici;Julio C Rojas;Howard J Rosen;Rowan Saloner;Adam Staffaroni;Gallen Triana-Baltzer;Salvatore Spina;William W Seeley;Lea T Grinberg;Hartmuth C Kolb;Renaud La Joie;Adam L Boxer - JAMA neurology (2025)
2. Diagnostic accuracy of plasma p-tau217/Aβ42 for Alzheimer’s disease in clinical and community cohorts. - Jun Wang;Shan Huang;Guoyu Lan;Yu-Jie Lai;Qing-Hua Wang;Yang Chen;Zhong-Song Xiao;Xiao Chen;Xian-Le Bu;Yu-Hui Liu;Fan Zeng;Laihong Zhang;Anqi Li;Yue Cai;Pan Sun;Zhengbo He;Vincent Doré;Jurgen Fripp;Pierrick Bourgeat;Qin Chen;Jin-Tai Yu;Yi Tang;Henrik Zetterberg;Colin L Masters;Tengfei Guo;Yan-Jiang Wang; - Alzheimer’s & dementia : the journal of the Alzheimer’s Association (2025)
3. New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race. - Lesley A Inker;Nwamaka D Eneanya;Josef Coresh;Hocine Tighiouart;Dan Wang;Yingying Sang;Deidra C Crews;Alessandro Doria;Michelle M Estrella;Marc Froissart;Morgan E Grams;Tom Greene;Anders Grubb;Vilmundur Gudnason;Orlando M Gutiérrez;Roberto Kalil;Amy B Karger;Michael Mauer;Gerjan Navis;Robert G Nelson;Emilio D Poggio;Roger Rodby;Peter Rossing;Andrew D Rule;Elizabeth Selvin;Jesse C Seegmiller;Michael G Shlipak;Vicente E Torres;Wei Yang;Shoshana H Ballew;Sara J Couture;Neil R Powe;Andrew S Levey; - The New England journal of medicine (2021)
4. Efficacy and safety of passive immunotherapies targeting amyloid beta in Alzheimer’s disease: A systematic review and meta-analysis. - Reina Tonegawa-Kuji;Yuan Hou;Bo Hu;Noah Lorincz-Comi;Andrew A Pieper;Babak Tousi;James B Leverenz;Feixiong Cheng - PLoS medicine (2025)
5. Preanalytical stability of plasma biomarkers for Alzheimer’s disease pathology. - Anita L Sunde;Ingvild V Alsnes;Dag Aarsland;Nicholas J Ashton;Diego A Tovar-Rios;Giovanni De Santis;Kaj Blennow;Henrik Zetterberg;Svein R Kjosavik - Alzheimer’s & dementia (Amsterdam, Netherlands) (2023)
6. Lecanemab in Early Alzheimer’s Disease. - Christopher H van Dyck;Chad J Swanson;Paul Aisen;Randall J Bateman;Christopher Chen;Michelle Gee;Michio Kanekiyo;David Li;Larisa Reyderman;Sharon Cohen;Lutz Froelich;Sadao Katayama;Marwan Sabbagh;Bruno Vellas;David Watson;Shobha Dhadda;Michael Irizarry;Lynn D Kramer;Takeshi Iwatsubo - The New England journal of medicine (2023)
7. The impact of kidney function on Alzheimer’s disease blood biomarkers: implications for predicting amyloid-β positivity. - Burak Arslan;Wagner S Brum;Ilaria Pola;Joseph Therriault;Nesrine Rahmouni;Jenna Stevenson;Stijn Servaes;Kübra Tan;Paolo Vitali;Maxime Montembeault;Jesse Klostranec;Arthur C Macedo;Cecile Tissot;Serge Gauthier;Juan Lantero-Rodriguez;Eduardo R Zimmer;Kaj Blennow;Henrik Zetterberg;Pedro Rosa-Neto;Andrea L Benedet;Nicholas J Ashton - Alzheimer’s research & therapy (2025)
8. Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology. - Nicholas J Ashton;Wagner S Brum;Guglielmo Di Molfetta;Andrea L Benedet;Burak Arslan;Erin Jonaitis;Rebecca E Langhough;Karly Cody;Rachael Wilson;Cynthia M Carlsson;Eugeen Vanmechelen;Laia Montoliu-Gaya;Juan Lantero-Rodriguez;Nesrine Rahmouni;Cecile Tissot;Jenna Stevenson;Stijn Servaes;Joseph Therriault;Tharick Pascoal;Alberto Lleó;Daniel Alcolea;Juan Fortea;Pedro Rosa-Neto;Sterling Johnson;Andreas Jeromin;Kaj Blennow;Henrik Zetterberg - JAMA neurology (2024)
9. Cohort Profile Update: The HUNT Study, Norway. - Bjørn Olav Åsvold;Arnulf Langhammer;Tommy Aune Rehn;Grete Kjelvik;Trond Viggo Grøntvedt;Elin Pettersen Sørgjerd;Jørn Søberg Fenstad;Jon Heggland;Oddgeir Holmen;Maria C Stuifbergen;Sigrid Anna Aalberg Vikjord;Ben M Brumpton;Håvard Kjesbu Skjellegrind;Pernille Thingstad;Erik R Sund;Geir Selbæk;Paul Jarle Mork;Vegar Rangul;Kristian Hveem;Marit Næss;Steinar Krokstad - International journal of epidemiology (2023)
10. Diagnosis of Alzheimer’s disease using plasma biomarkers adjusted to clinical probability. - Joseph Therriault;Shorena Janelidze;Andréa Lessa Benedet;Nicholas J Ashton;Javier Arranz Martínez;Armand Gonzalez-Escalante;Bruna Bellaver;Daniel Alcolea;Agathe Vrillon;Helmet Karim;Michelle M Mielke;Chang Hyung Hong;Hyun Woong Roh;José Contador;Albert Puig Pijoan;Alicia Algeciras-Schimnich;Prashanthi Vemuri;Jonathan Graff-Radford;Val J Lowe;Thomas K Karikari;Erin Jonaitis;Wagner Brum;Cécile Tissot;Stijn Servaes;Nesrine Rahmouni;Arthur C Macedo;Jenna Stevenson;Jaime Fernandez-Arias;Yi-Ting Wang;Marcel S Woo;Manuel A Friese;Wan Lu Jia;Julien Dumurgier;Claire Hourregue;Emmanuel Cognat;Pamela Lukasewicz Ferreira;Paolo Vitali;Sterling Johnson;Tharick A Pascoal;Serge Gauthier;Alberto Lleó;Claire Paquet;Ronald C Petersen;David Salmon;Niklas Mattsson-Carlgren;Sebastian Palmqvist;Erik Stomrud;Douglas Galasko;Sang Joon Son;Henrik Zetterberg;Juan Fortea;Marc Suárez-Calvet;Clifford R Jack;Kaj Blennow;Oskar Hansson;Pedro Rosa-Neto - Nature aging (2024)

© 2025 MaltSci - We reshape scientific research with AI technology