Journal Article

DZNE-2026-00552

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Blood phosphorylated tau elevation as a biomarker in immunoglobulin light chain and transthyretin amyloidosis.

Kaeser, S. A. (First author)DZNE* ; Schultz, S. A. ; Hofmann, A. (First author)DZNE* ; Häsler, L. M.DZNE* ; Xu, Y.DZNE* ; Lambert, M.DZNE* ; Obermüller, U.DZNE* ; Brockmann, K.DZNE* ; Bijzet, J. ; Nienhuis, H. ; Nuvolone, M. ; Obici, L. ; Palladini, G. ; Hegenbart, U. ; Schönland, S. O. ; Jucker, M. (Last author)DZNE*

2026
Springer Nature [New York, NY]

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Please use a persistent id in citations: doi:10.1038/s41591-026-04272-2

Abstract: Elevated blood levels of phosphorylated tau (p-tau) are diagnostic of Alzheimer disease and are associated with the deposition of amyloid-β in the cerebral neuropil. Elevated p-tau levels have also been associated with cerebral deposition of Danish amyloid and prion protein amyloid. Here we analyzed p-tau in serum from four different cohorts of people with the most common types of systemic amyloidosis, transthyretin (ATTR) amyloidosis and immunoglobulin light chain (AL) amyloidosis. We found higher levels of serum p-tau181 in the AL and ATTR groups than in controls. Subsequent analyses revealed that these effects were more pronounced in the presence of polyneuropathy (PNP) and in AL compared to ATTR amyloidosis. Individuals with different forms of PNP that were not due to amyloidosis did not exhibit elevated p-tau181 levels. In cases of presymptomatic (genetic) ATTR, p-tau181 levels increased as a function of predicted years from symptom onset. Additional measurement of p-tau217 in one cohort revealed similar increases, and discriminated people with AL and those with ATTR from controls equally as well as p-tau181. These findings suggest that elevated serum p-tau levels are not specific to Alzheimer disease and may also serve as a diagnostic tool of ATTR and AL amyloidosis, with potential utility in distinguishing amyloidosis-related PNP from PNP of other etiologies.

Keyword(s): Humans (MeSH) ; tau Proteins: blood (MeSH) ; Amyloid Neuropathies, Familial: blood (MeSH) ; Amyloid Neuropathies, Familial: diagnosis (MeSH) ; Biomarkers: blood (MeSH) ; Phosphorylation (MeSH) ; Female (MeSH) ; Male (MeSH) ; Immunoglobulin Light Chains: blood (MeSH) ; Middle Aged (MeSH) ; Aged (MeSH) ; Immunoglobulin Light-chain Amyloidosis: blood (MeSH) ; Cohort Studies (MeSH) ; Aged, 80 and over (MeSH) ; Alzheimer Disease: blood (MeSH) ; Adult (MeSH) ; tau Proteins ; Biomarkers ; Immunoglobulin Light Chains

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Contributing Institute(s):

1. Cell Biology of Neurological Diseases (AG Jucker)
2. Parkinson Genetics (AG Gasser)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)
2. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Nature ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 80 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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