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

Five human brains affected by Alzheimer's disease (AD), but without cerebel lar amyloid (A beta) deposits, were investigated for the presence and locat ion of amyloid precursor proteins (APP). This was parallel to 6 AD brains w ith A beta deposits, 6 young controls and 6 age-matched controls. Antibodie s against A beta 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 th e molecular layer were far greater than those in age-matched control brains and similar to those in AD brains with A beta deposits. This suggests that changes in APP production and/or metabolism occur before A beta deposition , or that these changes can occur without amyloidogenic processing. More th an 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 num ber (<21%) reacted with only a single antiserum. A small number of Golgi, L ugaro and granule cells were APP immunopositive. In all cases, stellate and basket cells were negative, as were most glial cells other than those of t he molecular layer. Folia showed two different appearances, which were part icularly well displayed in three cases: "strongly" immunopositive folia wit h high reactivity in Purkinje cells and other neurons, and "weakly" immunop ositive folia with low neuronal reactivity, but with a large number of posi tive glial cells in the molecular layer. The results are discussed in relat ion to the possible existence of types or stages of the AD process and loca l factors, including specific and non-specific cell factors, in the inducti on of APP accumulation. All these 5 cases were female, but the Apo-E 4 geno type was displayed only in two cases.