title: Correlations between mini-mental state examination score, cerebrospinal fluid biomarkers, and pathology observed in brain biopsies of patients with normal-pressure hydrocephalus.
abstract: Alzheimer disease (AD)-related pathology was assessed in cortical biopsy samples of 111 patients with idiopathic normal-pressure hydrocephalus. Alzheimer disease hallmark lesions-β-amyloid (Aβ) and hyperphosphorylated tau (HPtau)-were observed in 47% of subjects, a percentage consistent with that for whole-brain assessment reported postmortem in unselected cohorts. Higher-immunostained area fraction of AD pathology corresponded with lower preoperative mini-mental state examination scores. Concomitant Aβ and HPtau pathology, reminiscent of that observed in patients with AD, was observed in 22% of study subjects. There was a significant correlation between Aβ-immunostained area fraction in tissue and Aβ42 (42-amino-acid form of Aβ) in cerebrospinal fluid (CSF). Levels of Aβ42 were significantly lower in CSF in subjects with concomitant Aβ and HPtau pathology compared with subjects lacking pathology. Moreover, a significant correlation between HPtau-immunostained area fraction and HPtau in CSF was noted. Both HPtau and total tau were significantly higher in CSF in subjects with concomitant Aβ and HPtau pathology compared with subjects lacking pathology. The 42-amino-acid form of Aβ (Aβ42) and HPtau in CSF were the most significant predictors of the presence of AD pathology in cortical biopsies. Long-term follow-up studies are warranted to assess whether all patients with idiopathic normal-pressure hydrocephalus with AD pathology progress to AD and to determine the pathologic substrate of idiopathic normal-pressure hydrocephalus.
authors: From the Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå (KL); Department of Immunology, Genetics, and Pathology (AE, IA) and Division of Neurosurgery, Department of Neuroscience, Uppsala University (KGC); and Department of Pathology, Uppsala University Hospital (AE, IA), Uppsala, Sweden.
authors: Adila
authors: A
authors: Elobeid
authors: Katarina
authors: K
authors: Laurell
authors: Kristina Giuliana
authors: KG
authors: Cesarini
authors: Irina
authors: I
authors: Alafuzoff
mesh_terms: D000368:Aged; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D001706:Biopsy; D001921:Brain / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006850:Hydrocephalus, Normal Pressure / Q000134:cerebrospinal fluid* / Q000473:pathology*; D016015:Logistic Models; D008297:Male; D008609:Mental Status Schedule; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D012189:Retrospective Studies; D013223:Statistics as Topic; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins