{"doi":"10.1101/2022.04.10.22273671","title":"Elevated plasma phosphorylated tau 181 in amyotrophic lateral sclerosis relates to lower motor neuron dysfunction","abstract":"Abstract Objective Plasma phosphorylated tau (p-tau 181 ) is reliably elevated in Alzheimer’s disease (AD), but less explored is its specificity relative to other neurodegenerative conditions. Here we find novel evidence that plasma p-tau 181 is elevated in amytrophic lateral sclerosis (ALS), a neurodegenerative condition typically lacking tau pathology. We performed a detailed clinical evaluation to unravel the potential source of this unexpected observation. Methods Patients were clinically or pathologically diagnosed with ALS (n=130) or AD (n=82), or were healthy non-impaired controls (n=33). Receiver operating characteristic (ROC) curves were analyzed and area under the curve (AUC) was used to discriminate AD from ALS. Within ALS, Mann-Whitney-Wilcoxon tests compared analytes by presence/absence of upper motor neuron (UMN) and lower motor neuron (LMN) signs. Spearman correlations tested associations between plasma p-tau 181 and postmortem neuron loss. Results A Wilcoxon test showed plasma p-tau 181 was higher in ALS than controls (W=3297, p =0.0000020), and ROC analyses showed plasma p-tau 181 poorly discriminated AD and ALS (AUC=0.60). In ALS, elevated plasma p-tau 181 was associated with LMN signs in cervical (W=827, p =0.0072), thoracic (W=469, p =0.00025), and lumbosacral regions (W=851, p =0.0000029). In support of LMN findings, plasma p-tau 181 was associated with neuron loss in the spinal cord (rho=0.46, p =0.017), but not in the motor cortex ( p =0.41). CSF p-tau 181 and plasma neurofilament light chain (NfL) were included as reference analytes, and demonstrate specificity of findings. Interpretation We found strong evidence that plasma p-tau 181 is elevated in ALS and may be a novel marker specific to LMN dysfunction.","journal":"medRxiv","year":2022,"id":300008,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9518,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":27605,"name":"Leslie M. Shaw","orcid":"0000-0002-7650-1210","position":1,"is_corresponding":false},{"id":571366,"name":"Sanjana Shellikeri","orcid":"0000-0002-6436-292X","position":2,"is_corresponding":false},{"id":990235,"name":"Laynie Dratch","orcid":"0000-0002-2179-3199","position":3,"is_corresponding":false},{"id":578104,"name":"Luis Rosario","orcid":null,"position":4,"is_corresponding":false},{"id":495593,"name":"Lauren Elman","orcid":"0000-0003-4706-950X","position":5,"is_corresponding":false},{"id":226514,"name":"Colin Quinn","orcid":"0000-0003-0618-5854","position":6,"is_corresponding":false},{"id":625500,"name":"Defne A. Amado","orcid":"0000-0001-6202-3900","position":7,"is_corresponding":false},{"id":230045,"name":"David A. Wolk","orcid":"0000-0002-3554-3481","position":8,"is_corresponding":false},{"id":573957,"name":"Thomas F. Tropea","orcid":"0000-0003-0766-1496","position":9,"is_corresponding":false},{"id":76194,"name":"Alice S. Chen-Plotkin","orcid":"0000-0002-3387-2038","position":10,"is_corresponding":false},{"id":227417,"name":"David J. Irwin","orcid":"0000-0002-5599-5098","position":11,"is_corresponding":false},{"id":58510,"name":"Murray Grossman","orcid":"0000-0002-7447-6218","position":12,"is_corresponding":false},{"id":107087,"name":"Edward B. Lee","orcid":"0000-0002-4589-1180","position":13,"is_corresponding":false},{"id":27606,"name":"John Q. Trojanowski","orcid":"0000-0002-9239-8794","position":14,"is_corresponding":false},{"id":227422,"name":"Corey T. McMillan","orcid":"0000-0002-7581-6405","position":15,"is_corresponding":false},{"id":750910,"name":"Katheryn A Q Cousins","orcid":"0000-0003-1879-2766","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T00:31:49.412501Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}