Alzheimer's Disease CSF Biomarker Profiles in Idiopathic Normal Pressure Hydrocephalus

Patients with idiopathic normal pressure hydrocephalus (iNPH) frequently show pathologic CSF Aβ₄₂ levels, comparable with Alzheimer's Disease (AD). Nevertheless, the clinical meaning of these findings has not been fully explained. We aimed to assess the role of AD CSF biomarkers (Aβ₄₂, Aβ₄₂/Aβ₄₀, p-tau, t-tau) in iNPH. To this purpose, we enrolled 44 patients diagnosed with iNPH and 101 with AD. All the patients underwent CSF sampling. We compared CSF biomarker levels in iNPH and AD: Aβ₄₂ levels were not different between iNPH and AD, while Aβ₄₂/Aβ₄₀, p-tau, and t-tau were significantly different and showed excellent accuracy in distinguishing iNPH and AD. A multiple logistic regression analysis showed that Aβ₄₂/Aβ₄₀ was the variable that most contributed to differentiating the two groups. Furthermore, iNPH patients with positive Aβ₄₂/Aβ₄₀ had higher p-tau and t-tau than iNPH patients with negative Aβ₄₂/Aβ₄₀. Those iNPH patients who showed cognitive impairment had lower Aβ₄₂/Aβ₄₀ and higher p-tau than patients without cognitive impairment. We concluded that positive CSF Aβ₄₂ with negative Aβ₄₂/Aβ₄₀, p-tau, and t-tau is a typical CSF profile of iNPH. On the contrary, positive Aβ₄₂/Aβ₄₀ in iNPH patients, especially when associated with positive p-tau, may lead to suspicion of a coexistent AD pathology.