guest ::
| Home > Publications Database > Alzheimer's Disease Co-Pathology and Cognitive Impairment in Amyotrophic Lateral Sclerosis. |
| Home > Publications Database > Alzheimer's Disease Co-Pathology and Cognitive Impairment in Amyotrophic Lateral Sclerosis. |
| Journal Article | DZNE-2026-00692 |
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ;
2026
Wiley-Blackwell
Hoboken, NJ
This record in other databases: 
Please use a persistent id in citations: doi:10.1002/ana.78227
Abstract: Amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) share neuropathological features, including tau, amyloid, and TDP-43 pathology. This study investigated whether AD-related pathological changes are associated with cognitive impairment ALS.Cerebrospinal fluid (CSF total-tau, phosphorylated-tau, beta-amyloid) and plasma biomarkers (TDP-43; neurofilament light chain [NfL]) were analyzed in 192 individuals with ALS or ALS with frontotemporal dementia (ALS-FTD) and 100 healthy controls. Cognitive performance was assessed using the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). Group comparisons and regression analyses examined associations between biomarker profiles and cognitive status. Autopsy data were available for a subset of participants.Compared with healthy controls, patients with ALS - particularly those with cognitive impairment (ALSci) or ALS-FTD - showed elevated AD-related biomarkers. Significant differences in beta-amyloid levels were observed between healthy controls (HCs) and patients with ALSci, but not between controls and cognitively unimpaired patients. CSF p-tau and total-tau levels were strongly associated with domain-specific cognitive performance. In contrast, plasma extracellular vesicle TDP-43 and NfL showed weak or no association with cognition. In vivo biomarkers alone reliably distinguished cognitive impairment only in ALSci and ALS-FTD. Postmortem analyses showed no strong association between ABC scores or overall TDP-43 burden and cognitive state; however, temporal and hippocampal TDP-43 burden was associated with cognitive dysfunction.Our findings suggest that tau-related CSF biomarkers, particularly p-tau and total-tau, are associated with cognitive deficits in ALS, indicating that AD-related pathology might be associated to cognitive decline in ALS. However, postmortem data showed even stronger relation of TDP43 pathology to cognitive deficits in ALS. ANN NEUROL 2026;100:123-138.
Keyword(s): Humans (MeSH) ; Amyotrophic Lateral Sclerosis: pathology (MeSH) ; Amyotrophic Lateral Sclerosis: complications (MeSH) ; Amyotrophic Lateral Sclerosis: cerebrospinal fluid (MeSH) ; Amyotrophic Lateral Sclerosis: psychology (MeSH) ; Female (MeSH) ; Male (MeSH) ; Alzheimer Disease: pathology (MeSH) ; Alzheimer Disease: complications (MeSH) ; Alzheimer Disease: cerebrospinal fluid (MeSH) ; tau Proteins: cerebrospinal fluid (MeSH) ; Aged (MeSH) ; Cognitive Dysfunction: pathology (MeSH) ; Cognitive Dysfunction: cerebrospinal fluid (MeSH) ; DNA-Binding Proteins: blood (MeSH) ; DNA-Binding Proteins: cerebrospinal fluid (MeSH) ; Amyloid beta-Peptides: cerebrospinal fluid (MeSH) ; Middle Aged (MeSH) ; Biomarkers: cerebrospinal fluid (MeSH) ; Biomarkers: blood (MeSH) ; Neurofilament Proteins: cerebrospinal fluid (MeSH) ; Neurofilament Proteins: blood (MeSH) ; Frontotemporal Dementia: pathology (MeSH) ; tau Proteins ; DNA-Binding Proteins ; Amyloid beta-Peptides ; Biomarkers ; TARDBP protein, human ; Neurofilament Proteins ; neurofilament protein L
; 
; 
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; Nationallizenz
; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
PDF
PDF (PDFA)