Comparative Methods for Quantifying Plasma Biomarkers in Alzheimer's Disease: Implications for the Next Frontier in Cerebral Amyloid Angiopathy Diagnostics

Overview

Journal Alzheimers Dement

Specialties Neurology
Psychiatry

Date 2023 Nov 1

PMID 37908054

Authors

Ryan T Muir

Zahinoor Ismail

Sandra E Black

Eric E Smith

Affiliations

Soon will be listed here.

Abstract

Plasma amyloid beta (Aβ) and tau are emerging as accessible biomarkers for Alzheimer's disease (AD). However, many assays exist with variable test performances, highlighting the need for a comparative assessment to identify the most valid assays for future use in AD and to apply to other settings in which the same biomarkers may be useful, namely, cerebral amyloid angiopathy (CAA). CAA is a progressive cerebrovascular disease characterized by deposition of Aβ and Aβ in cortical and leptomeningeal vessels. Novel immunotherapies for AD can induce amyloid-related imaging abnormalities resembling CAA-related inflammation. Few studies have evaluated plasma biomarkers in CAA. Identifying a CAA signature could facilitate diagnosis, prognosis, and a safer selection of patients with AD for emerging immunotherapies. This review evaluates studies that compare the diagnostic test performance of plasma biomarker techniques in AD and cerebrovascular and plasma biomarker profiles of CAA; it also discusses novel hypotheses and future avenues for plasma biomarker research in CAA.

Citing Articles

Circulating proteomic biomarkers for cerebral amyloid angiopathy screening and risk stratification.

Xu J, Su Y, Sha Y, Fu J, Yan T, Xu F Alzheimers Dement. 2025; 21(3):e70044.

PMID: 40042503 PMC: 11881623. DOI: 10.1002/alz.70044.

Plasma Phosphorylated Tau 217 as a Discriminative Biomarker for Cerebral Amyloid Angiopathy.

Hsieh P, Tsai H, Liu C, Lee B, Tsai Y, Yen R Eur J Neurol. 2025; 32(2):e70066.

PMID: 39907306 PMC: 11795418. DOI: 10.1111/ene.70066.

Decoding Neurodegeneration: A Review of Molecular Mechanisms and Therapeutic Advances in Alzheimer's, Parkinson's, and ALS.

Toader C, Tataru C, Munteanu O, Serban M, Covache-Busuioc R, Ciurea A Int J Mol Sci. 2024; 25(23.

PMID: 39684324 PMC: 11641752. DOI: 10.3390/ijms252312613.

Analysis of Speech Features in Alzheimer's Disease with Machine Learning: A Case-Control Study.

Noto S, Sekiyama Y, Nagata R, Yamamoto G, Tamura T Healthcare (Basel). 2024; 12(21).

PMID: 39517405 PMC: 11545255. DOI: 10.3390/healthcare12212194.

Alzheimer's diagnosis beyond cerebrospinal fluid: Probe-Free Detection of Tau Proteins using MXene based redox systems and molecularly imprinted polymers.

Arjun A, Deshpande S, Dunlop T, Norman B, Oliviera D, Vulpe G Biosens Bioelectron X. 2024; 20:100513.

PMID: 39355372 PMC: 11406148. DOI: 10.1016/j.biosx.2024.100513.

References

Janelidze S, Palmqvist S, Leuzy A, Stomrud E, Verberk I, Zetterberg H . Detecting amyloid positivity in early Alzheimer's disease using combinations of plasma Aβ42/Aβ40 and p-tau. Alzheimers Dement. 2021; 18(2):283-293. DOI: 10.1002/alz.12395. View

Smith E, Greenberg S . Beta-amyloid, blood vessels, and brain function. Stroke. 2009; 40(7):2601-6. PMC: 2704252. DOI: 10.1161/STROKEAHA.108.536839. View

Weksler M, Relkin N, Turkenich R, LaRusse S, Zhou L, Szabo P . Patients with Alzheimer disease have lower levels of serum anti-amyloid peptide antibodies than healthy elderly individuals. Exp Gerontol. 2002; 37(7):943-8. DOI: 10.1016/s0531-5565(02)00029-3. View

Verberk I, Thijssen E, Koelewijn J, Mauroo K, Vanbrabant J, de Wilde A . Combination of plasma amyloid beta and glial fibrillary acidic protein strongly associates with cerebral amyloid pathology. Alzheimers Res Ther. 2020; 12(1):118. PMC: 7523295. DOI: 10.1186/s13195-020-00682-7. View

Preische O, Schultz S, Apel A, Kuhle J, Kaeser S, Barro C . Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease. Nat Med. 2019; 25(2):277-283. PMC: 6367005. DOI: 10.1038/s41591-018-0304-3. View

Schindler S, Bollinger J, Ovod V, Mawuenyega K, Li Y, Gordon B . High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis. Neurology. 2019; 93(17):e1647-e1659. PMC: 6946467. DOI: 10.1212/WNL.0000000000008081. View

Jianping L, Zhibing Y, Wei Q, Zhikai C, Jie X, Jinbiao L . Low avidity and level of serum anti-Abeta antibodies in Alzheimer disease. Alzheimer Dis Assoc Disord. 2006; 20(3):127-32. DOI: 10.1097/00002093-200607000-00001. View

Lam B, Masellis M, Freedman M, Stuss D, Black S . Clinical, imaging, and pathological heterogeneity of the Alzheimer's disease syndrome. Alzheimers Res Ther. 2013; 5(1):1. PMC: 3580331. DOI: 10.1186/alzrt155. View

Janelidze S, Teunissen C, Zetterberg H, Allue J, Sarasa L, Eichenlaub U . Head-to-Head Comparison of 8 Plasma Amyloid-β 42/40 Assays in Alzheimer Disease. JAMA Neurol. 2021; 78(11):1375-1382. PMC: 8453354. DOI: 10.1001/jamaneurol.2021.3180. View

10.

Verberk I, Laarhuis M, van den Bosch K, Ebenau J, van Leeuwenstijn M, Prins N . Serum markers glial fibrillary acidic protein and neurofilament light for prognosis and monitoring in cognitively normal older people: a prospective memory clinic-based cohort study. Lancet Healthy Longev. 2022; 2(2):e87-e95. DOI: 10.1016/S2666-7568(20)30061-1. View

11.

Storace D, Cammarata S, Borghi R, Sanguineti R, Giliberto L, Piccini A . Elevation of {beta}-amyloid 1-42 autoantibodies in the blood of amnestic patients with mild cognitive impairment. Arch Neurol. 2010; 67(7):867-72. DOI: 10.1001/archneurol.2010.137. View

12.

Su Y, Flores S, Wang G, Hornbeck R, Speidel B, Joseph-Mathurin N . Comparison of Pittsburgh compound B and florbetapir in cross-sectional and longitudinal studies. Alzheimers Dement (Amst). 2019; 11:180-190. PMC: 6389727. DOI: 10.1016/j.dadm.2018.12.008. View

13.

Olsson B, Lautner R, Andreasson U, Ohrfelt A, Portelius E, Bjerke M . CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis. Lancet Neurol. 2016; 15(7):673-684. DOI: 10.1016/S1474-4422(16)00070-3. View

14.

Guo Y, Shen X, Huang S, Chen S, Wang H, Zhang W . Head-to-head comparison of 6 plasma biomarkers in early multiple system atrophy. NPJ Parkinsons Dis. 2023; 9(1):40. PMC: 10017699. DOI: 10.1038/s41531-023-00481-5. View

15.

Vergallo A, Megret L, Lista S, Cavedo E, Zetterberg H, Blennow K . Plasma amyloid β 40/42 ratio predicts cerebral amyloidosis in cognitively normal individuals at risk for Alzheimer's disease. Alzheimers Dement. 2019; 15(6):764-775. DOI: 10.1016/j.jalz.2019.03.009. View

16.

Zetterberg H . Neurofilament Light: A Dynamic Cross-Disease Fluid Biomarker for Neurodegeneration. Neuron. 2016; 91(1):1-3. DOI: 10.1016/j.neuron.2016.06.030. View

17.

Li Y, Schindler S, Bollinger J, Ovod V, Mawuenyega K, Weiner M . Validation of Plasma Amyloid-β 42/40 for Detecting Alzheimer Disease Amyloid Plaques. Neurology. 2021; 98(7):e688-e699. PMC: 8865895. DOI: 10.1212/WNL.0000000000013211. View

18.

Chatterjee P, Elmi M, Goozee K, Shah T, Sohrabi H, Dias C . Ultrasensitive Detection of Plasma Amyloid-β as a Biomarker for Cognitively Normal Elderly Individuals at Risk of Alzheimer's Disease. J Alzheimers Dis. 2019; 71(3):775-783. DOI: 10.3233/JAD-190533. View

19.

Koemans E, Chhatwal J, van Veluw S, van Etten E, van Osch M, van Walderveen M . Progression of cerebral amyloid angiopathy: a pathophysiological framework. Lancet Neurol. 2023; 22(7):632-642. DOI: 10.1016/S1474-4422(23)00114-X. View

20.

Wardlaw J, Benveniste H, Nedergaard M, Zlokovic B, Mestre H, Lee H . Perivascular spaces in the brain: anatomy, physiology and pathology. Nat Rev Neurol. 2020; 16(3):137-153. DOI: 10.1038/s41582-020-0312-z. View