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Jusak Nugraha
Clinical Pathology Department, Dr. Soetomo Hospital Surabaya Institute Of Tropical Disease, Universitas Airlangga Surabaya
Agriculture, Biological Sciences & Forestry Biochemistry, Genetics & Molecular Biology Chemistry Decision Sciences, Operations Research & Management Dentistry Earth & Planetary Sciences Health Professions Immunology & microbiology Medicine & Pharmacology Neuroscience Public Health Veterinary Other

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Associations between plasma beta amyloid and cognitive decline: A systematic review and meta-analysis Cynthia, Cynthia; Nugraha, Jusak; Hamdan, Muhammad; Dharma, Rahajuningsih; Lumempouw, Silvia F.
Narra J Vol. 5 No. 2 (2025): August 2025
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v5i2.2268

Abstract

Alzheimer’s disease is a leading neurodegenerative disorder characterized by progressive cognitive decline. Early prediction is crucial for enabling timely interventions. Plasma amyloid β-peptides (Aβ), particularly the Aβ-42/Aβ-40 ratio, have been proposed as potential non-invasive biomarkers for cognitive decline and Alzheimer’s disease risk. However, conflicting findings and methodological variability have hindered consensus regarding their clinical utility. The aim of this study was to evaluate whether the plasma Aβ levels predict dementia, Alzheimer’s disease, and cognitive decline. Studies were eligible for inclusion if they measured at least one plasma Aβ species (Aβ-40, Aβ-42, or the Aβ-42/Aβ-40 ratio) and reported outcomes related to dementia, Alzheimer’s disease, or cognitive change. Only human studies published in peer-reviewed journals were included. A comprehensive search of six databases (PubMed, PMC, SSRN, Scopus, BioRxiv, and MedRxiv) was conducted up to December 1, 2024. Risk of bias was assessed using the ROBINS-E tool, and pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random-effects meta-analysis. A total of 25 studies were included in the systematic review, with four contributing to the meta-analysis. Lower plasma Aβ-42/Aβ-40 ratio was not significantly associated with Alzheimer’s disease risk (pooled HR=0.8; 95%CI: 0.62–1.04), and substantial heterogeneity was observed (I²=70%, p=0.02). Individual studies varied in their findings: while some reported that lower Aβ-42/Aβ-40 ratio predicted increased Alzheimer’s disease risk, others found no association or even opposing trends. Methodological heterogeneity—including differences in sample handling, measurement techniques, and study designs—likely contributed to these inconsistencies. Overall, this review suggests that plasma Aβ-42/Aβ-40 ratio is not reliable predictors for the onset of Alzheimer’s disease or dementia. However, the substantial heterogeneity observed underscores the need for further research to clarify the potential of plasma Aβ as a preclinical biomarker.
Co-Authors Abdul Hafid B Agung Dwi Wahyu W Agung Dwi Wahyu Widodo Agustiningrum, Indah Akhmad Setyo Rahman aminuddin, mohammad Anak Agung Istri Sri Wiadnyani Anita Budiarti Anna Roosdiana Anton Yuntarso Aryati Aryati Aryati Aryati Ashon Sa'adi Ashon Sa’adi Ashon Sa’adi Awalia Awalia Ayu Imamatun Nisa Bambang Purwanto Bastian Bastian Bastian Bastian Beatrix, Stephanie Besin, Valentinus Betty Agustina Betty Agustina Tambunan Buana, Dwi Candra Budi Prasetyo Budi Utomo Budiutari, Ni Nyoman Budy, Theresia Indah Callixte, Cyuzuzo Caroline Caroline Ch. Destri Wiwis Wijayanti Christina Destri Citra Indah Setyaningrum Cynthia Cynthia Cynthia Cyuzuzo Callixte Darmadi, Epriyanto T Dheasy Herawati Diyan Wahyu Kurniasari Djoko Agus Purwanto Dominicus Husada Dwi Aris Agung Nugrahaningsih Dwi Liliek Kusindarta Dwiyanti Puspitasari, Dwiyanti Eddy Mart Salim Eddy Mart Salim Eddy Mart Salim Eddy Mart Salim, Eddy Mart Edhi Rianto Elok Budi Retnani Elvan Dwi Widyadi Erfina Lim Erna R Tobing Esthy Poespitaningtyas Febtarini Rahmawati Ferdy R. Marpaung Ferdy Royland Marpaung Foe, Kuncoro Francisca Srioetami Tanoerahardjo Francisca Srioetami Tanoerahardjo Fransisca Srioetami Tanoerahardjo Fransisca Srioetami Tanoerahardjo Fransiska Fransiska Fransiska Sri Oetami Gede Arie Wijaya Handayani, Luh Putu Trys Monika Hans Kristian Nugraha, Hans Kristian Hantoro Gunawan Hari Basuki Notobroto Hari Setiono Hartono Kahar, Hartono Hendy Wijaya Herin Mawarti Heru Setiawan Hery Priyanto Hevi Wihadmadyatami Holland Lydia Marpaung Huda Shalahudin Darusman I Made Andika Bara Kusuma Idha Kusumawati Ilham Ilham Irvan Ipandi Januarti, Catur Ifda Joewono Soeroso John Wiwin Julious Julious julious, julious Kasiyati, Menik Kemas Ya'kub Rahadiyanto Kemas Ya'kub Rahadiyanto Kemas Ya’kub Rahadiyanto kurniati, nova Lisa Soegianto Lumempouw, Silvia Luminto, Dian Lutfi Dewanda Nugroho M. Aminuddin M. Aminuddin M. Irsan Saleh Maya E. Roring Meiti Muljanti, Meiti Mohammad Aminuddin Mohammad Hasan Machfoed Muhammad Amin Muhammad Amminuddin Muhammad Hamdan Muhammad Irsan Saleh Muhammad Nazarudin Munawaroh Fitriah Myrza Elita Nico Jafet Ningrum, Emilna Mega Ninik Asmaningsih Soemyarso Notopuro, Paulus Budiono Nova Kurniati Nova Kurniati Nova Kurniati Noviana, Rachmitasari Nugraha, Hans K Nur Hayati Nur Lailatul Fadhilah Oetami, Fransisca Sri Oryza Chrisantia Patria Dewi Pande Pratama, Dyah Ayu Oktaviani A Prihantika S., Sabrina Pudji Lestari Purwanta, Marijam Purwoko, Agus Puspitasari, Yessy Putri, Indah Aprianti Rahadiyanto, Kemas Ya'Kub Rahajuningsih Dharma Rahma Indah Pratiwi Rendy, Achmad Nur Rifa’I, Muh Husni Risky V. Prasetyo Roedi Irawan Rusli, Musofa Ryzky Widi Atmaja S. Soedarsono S.Pd. M Kes I Ketut Sudiana . Sabri Prihantika Sabrina Prihantika Saleh, M Irsan Saputra, Angky Saputri, Agatha Efrad Senny Yesery Esar Setiawan, Lidwina Tri Kristanti Shahzad Shoukat Sheila Clarissa Shoukat, Hamad Shoukat, Shahzad SILMI MARIYA Silvia F. Lumempouw Sinansari, Restry Siti Nur Husnul Yusmiati Siti Rahmawati Soedarsono Soedarsono Soedarsono Soedarsono Soelistijo, Soebagijo Adi SP Edijanto Srikanth Karnati Süleyman Ergün Susi Oktaviani Tanoehardjo, Francisca Srioetami Tanoehardjo, Francisca Srioetami Tanoerahardjo, Francisca Srioetami Tedja, I G.A. Wiradari Theresia Indah Budhy Sulisetyawati Triagung Ruddy Tuyishimire Irene Utariani, Arie UUS SAEPULOH Wahyu Dewi Tamayanti, Wahyu Dewi Wahyu Setiani Wibowo Wahyu Setiani Wibowo Winthoko, Eka Nora Vitaloka Aprilia Putri Wulandari, Dian Novita Wuryanto Hadinugroho Yetti Hernaningsih Yoes Prijatna Dachlan Yudy Tjahjono Yufita Ratnasari Wilianto Yulia Nadar Indrasari Zen Hafy