Amyloid precursor proteins in the cerebellar cortex of Alzheimer's disease patients devoid of cerebellar β-amyloid deposits: immunocytochemical study of five cases

Summary.

Five human brains affected by Alzheimer's disease (AD), but without cerebellar amyloid (Aβ) deposits, were investigated for the presence and location of amyloid precursor proteins (APP). This was parallel to 6 AD brains with Aβ deposits, 6 young controls and 6 age-matched controls. Antibodies against Aβ and two epitopes of APP (amino and carboxy terminals, APP_60–100 and APP_643–695, respectively) were employed. Accumulations of APP in neurons (mainly Purkinje cells) and glial cells in the upper part of the molecular layer were far greater than those in age-matched control brains and similar to those in AD brains with Aβ deposits. This suggests that changes in APP production and/or metabolism occur before Aβ deposition, or that these changes can occur without amyloidogenic processing. More than 60% of positive Purkinje neurons were of normal appearance; most of them showed both APP_60–100 and APP_643–695 immunoreactivity, but a small number (<21%) reacted with only a single antiserum. A small number of Golgi, Lugaro and granule cells were APP immunopositive. In all cases, stellate and basket cells were negative, as were most glial cells other than those of the molecular layer. Folia showed two different appearances, which were particularly well displayed in three cases: "strongly" immunopositive folia with high reactivity in Purkinje cells and other neurons, and "weakly" immunopositive folia with low neuronal reactivity, but with a large number of positive glial cells in the molecular layer. The results are discussed in relation to the possible existence of types or stages of the AD process and local factors, including specific and non-specific cell factors, in the induction of APP accumulation. All these 5 cases were female, but the Apo-E 4 genotype was displayed only in two cases.