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

Patients with idiopathic normal pressure hydrocephalus (iNPH) frequently show pathologic CSF Aβ(42) 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 (Aβ(42), Aβ(42)/Aβ(40), 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: Aβ(42) levels were not different between iNPH and AD, while Aβ(42)/Aβ(40), p-tau, and t-tau were significantly different and showed excellent accuracy in distinguishing iNPH and AD. A multiple logistic regression analysis showed that Aβ(42)/Aβ(40) was the variable that most contributed to differentiating the two groups. Furthermore, iNPH patients with positive Aβ(42)/Aβ(40) had higher p-tau and t-tau than iNPH patients with negative Aβ(42)/Aβ(40). Those iNPH patients who showed cognitive impairment had lower Aβ(42)/Aβ(40) and higher p-tau than patients without cognitive impairment. We concluded that positive CSF Aβ(42) with negative Aβ(42)/Aβ(40), p-tau, and t-tau is a typical CSF profile of iNPH. On the contrary, positive Aβ(42)/Aβ(40) in iNPH patients, especially when associated with positive p-tau, may lead to suspicion of a coexistent AD pathology.