P75 neurotrophin receptor in the nucleus basalis of Meynert in relation toage, sex, and Alzheimer's disease

In a previous study we showed that the staining of tyrosine kinase receptor s (trks), which are high-affinity neurotrophin receptors (NTRs), is strongl y diminished in the nucleus basalis of Meynert (NBM) of Alzheimer's disease (AD) patients, which may explain the lack of effect of NGF therapy in AD p atients so far. Since the literature regarding the expression of low-affini ty NTRs was rather controversial, the aim of the present study was to exami ne (i) possible changes in the staining of low-affinity NTRs, i.e., p75 in the human NBM, an area that is severely affected in AD; and (ii) alteration s of these receptors in relation to risk factors for AD, e.g., age, sex, an d menopause. Brain material of 31 controls and 30 AD patients was obtained at autopsy, embedded in paraffin, and stained immunocytochemically. Using a n image analysis system, we quantified p75 immunoreactivity in both cell bo dies and fibers at the level of the NBM. Our results showed a significant d iminishment of p75 immunoreactivity in both cell bodies and fibers of NBM n eurons in AD. We did not find any relationship between age or sex and the e xpression of p75 receptor in cell bodies. However, there was a clearly posi tive relationship between age and fiber staining in AD patients which sugge sts the occurrence of a p75 transport disorder as an early event in the pro cess of AD, These observations and the earlier reported decreased staining of trk receptors show that degeneration of NBM neurons in AD is associated with a decreased neurotrophin responsiveness of NBM neurons in AD and that therapeutic strategies should be directed toward upregulation of receptors or facilitation of transport before an effect of neurotrophins in AD may be expected. (C) 2000 Academic Press.