A cortical biopsy was analyzed using immunohistochemical methodology in a total of 213 patients with suspected normal pressure hydrocephalus (NPH). Normal intracranial pressure (ICP) was registered in 121 (43 %) of patients with suspected NPH. The incidence of Alzheimer's disease (AD) related lesions was quite high, since 38 % of all subjects displayed beta-amyloid (betaA4) aggregates and in 8 % of subjects paired helical filament-tau (PHF-tau) pathology was noted. The AD associated pathologies were more common in subjects with normal than elevated ICP. Of the 121 subjects with NPH, 16 (13 %) had subclinical, histopathologically verified AD and a further 40 subjects (33 %) could be considered to be at high risk to develop AD. Pharmacological treatment trials of AD should be carried out on subjects with evident brain pathology (betaA4 aggregates or PHF-tau pathology) especially during the early stage of the disease, i.e., the subclinical stage. For this purpose a simple cortical biopsy with a low risk of complication would represent a diagnostic "method" of choice.