Neurofilament-immunoreactive neurons are not selectively vulnerable in Alzheimer's disease

Abnormal neurofilament protein distribution and phosphorylation contributes to the cytoskeletal pathology of Alzheimer's disease. Anatomical studies s uggest that cortical neurons immunoreactive for nonphosphorylated 200-kDa n eurofilament are most vulnerable. We repeated these studies in formalin-fix ed temporal robe tissue from five Alzheimer's disease cases with tissue vol ume loss compared to five controls without tissue loss. Immunohistochemistr y for nonphosphorylated and phosphorylated forms of the neurofilament prote in was counterstained for Nissl substance and immune-positive and -negative pyramidal neurons quantified using areal fraction counts. Compared with co ntrols, cases with Alzheimer's disease had similar numbers of neurons expre ssing the nonphosphorylated neurofilament protein, suggesting these neurons are largely spared by the disease process. In Alzheimer's disease there wa s a significant increase in neurons containing phosphorylated neurofilament and tau proteins and a decrease in neurons devoid of neurofilament protein . Our results challenge the theory that neurons containing 200 kDa neurofil ament are selectively vulnerable in Alzheimer's disease. (C) 2001 Academic Press.