AUTOMATED IDENTIFICATION AND QUANTITATIVE MORPHOMETRY OF THE SENILE PLAQUES OF ALZHEIMERS-DISEASE

OBJECTIVE: Senile plaques (SP) are one of the characteristic neuropath ologic lesions of Alzheimer's Disease (AD), and studies of SP cortical distribution, density and morphology may lead to new information abou t the mechanism and pathogenesis of AD. We used an automated, digital image analysis program to detect and measure SP size, shape and total fractional area in digital images of silver-stained tissue sections. S TUDY DESIGN: The program observed 94,000 SP in 2,800 digitized microsc ope fields from tissue sections from 42 postmortem cases ranging from healthy aged to severely demented subjects, studied prospectively befo re death. RESULTS: Automated pattern recognition can measure SP densit ies in excellent agreement with an expert and can generate morphometri c information not obtainable by conventional microscopy. SP densities (number of SPs/mm(2)) strongly correlate with tissue load (fraction of tissue area occupied by lesions). SP densities strongly correlate bet ween cortical regions within the same subjects. SP densities, while co rrelating with the occurrence of AD, do not display a significant tren d with respect to dementia severity; likewise, mean SP area and shape properties do not vary significantly with dementia severity. Finally, all the computed SP densities would have produced the same diagnoses o f AD in these subjects Its the manual SP densities according to the co nsensus criteria. CONCLUSION: This is the first fully automated progra m to identify SPs and measure SP morphometry; it uses well-established digital image analysis and statistical pattern recognition methods. T he computed SP densities correlate highly with expert results, and the systematic differences are smaller than the interrater differences re ported in several multicenter Alzheimer's disease neuropathology studi es. The program measures morphometric properties that would be impract ical to measure by manual means and, with program-controlled, scanning stage microscopy, can measure lesion densities exhaustively across la rge cortical areas without stereologic sampling. SP densities rise fro m near zero to significant values at the mildest diagnosed stage of AD , but beyond this point, there is no demonstrable correlation of densi ty, or any other SP property, with dementia severity. Computed SP dens ities for even the mildest dementia satisfy the consensus diagnostic c riteria.