Tau protein and apolipoprotein E are suggested to be biochemically related to neurofibrillary tangles and senile plaques in Alzheimer's disease (AD) brains. They can be detected as immunoreactive material (total tau immunoreactivity [TTIR] and apolipoprotein E-immunoreactivity [ApoEIR]) in the cerebrospinal fluid (CSF). TTIR and ApoE-IR have been measured in ex vivo lumbar and post mortem ventricular CSF in AD, other neurological diseases without cognitive impairment, elderly depressive patients, and young and elderly controls. In lumbar CSF, there was a highly significant increase of TTIR and a minor, insignificant decrease of ApoE-IR in CSF of AD patients. The latter result was also found in ventricular CSF, whereas TTIR showed no significant difference between groups in the rostral CSF compartment. As depressive periods in the elderly may mimick a dementing process, these findings contribute to the differential diagnosis of these disorders by showing a different neurobiochemical CSF profile. Work in progress will include a variety of non-Alzheimer's dementias and possibly will further increase the value of CSF investigation in neurodegenerative disorders.