Accumulation of calbindin in cortical pyramidal cells with ageing; a putative protective mechanism which fails in Alzheimer's disease

There is considerable interest in the status of calbindin immunoreactive ne urones in Alzheimer's disease (AD) but previous studies have produced widel y differing results. Here we describe calbindin neurones in temporal neocor tex from 18 severely demented patients with neuropathologically confirmed A D and 13 age and post-mortem delay matched, neurologically normal controls. Calbindin immunoreactive neurones were small and round in layers II-IV, an d pyramidal in layers IIIc and V. There were significantly more calbindin p ositive neurones in controls than in AD (mean +/- SD, for each comparison P <0.01): superior temporal lobe, AD=3.32<plus/minus>2.24, Control (C) =24.83 +/- 10.8; middle temporal lobe, AD = 3.6 +/-4.94, C=26.09 +/- 15.7; inferi or temporal lobe, AD 3.69 +/-3.6. C=25.25 +/- 16.9. Furthermore, there was an age-related increase in immunopositive neurones in the superior (r(2)=0. 37, P=0.046) and inferior (r(2)=0.75, P=0.01) temporal gyri in controls. In AD the number of calbindin positive neurones did not change with age. This is the first report of such an age-related increase in controls, and it su ggests that this, rather than a decrease in AD, accounts for the overall di fference between AD and controls. It is possible that an increase in intran euronal calbindin protects these cells from degeneration and that failure o f such a neuroprotective mechanism is a significant contributory factor in the pathogenesis of AD.