The paper reports routine incorporation of AD CSF biomarkers and alpha-synuclein skin biopsy into iNPH evaluations, finding ~32% AD-consistent CSF profiles and ~31% biopsy-confirmed alpha-synuclein pathology among patients.

Identifying coexisting alpha-synuclein pathology is directly relevant to Parkinson's research because it supports use of peripheral biomarkers for patient stratification and trial enrichment, reducing confounding by mixed pathology even though the study does not propose new therapeutic mechanisms.

Idiopathic normal pressure hydrocephalus (iNPH), characterized by ventriculomegaly and Hakim's triad of gait disturbance, cognitive impairment, and urinary dysfunction, is common in older adults. iNPH also remains one of the few potentially reversible neurological conditions, typically treated with cerebrospinal fluid (CSF) shunting. Although many patients improve, shunt responsiveness varies widely (≈60%-90%), and a subset of patients show only transient benefit. A major contributor to this variability is the high prevalence of comorbid neurodegenerative disease with symptom overlap, particularly Alzheimer's disease (AD) and α-synucleinopathies such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The impact of these concomitant conditions on shunt outcomes, however, remains uncertain. We describe the incorporation of AD CSF biomarkers and α-synuclein skin biopsy into the iNPH evaluation to identify coexisting pathology. When integrated into routine workflow, approximately 32% of patients demonstrated AD-consistent CSF profiles and 31% had biopsy-confirmed α-synuclein pathology. We propose adopting concomitant neurological testing, especially in patients with atypical features to help inform patient selection and guide expectations. As the awareness and potential prevalence of iNPH rises and shunt procedures carry meaningful complication risks, delineating how comorbid disease modifies outcomes will be essential to improving the long-term success of shunting in iNPH.