MULTIVARIATE-ANALYSIS OF LAMINAR PATTERNS OF NEURODEGENERATION IN POSTERIOR CINGULATE CORTEX IN ALZHEIMERS-DISEASE

Posterior cingulate cortex is the site of earliest reductions in gluco se metabolism and qualitatively different laminar patterns of neurodeg eneration in Alzheimer's disease (AD). This study used multivariate an alyses of area 23 in 72 cases of definite AD to assess relationships b etween laminar patterns of neurodegeneration, neurofibrillary tangle ( NFT) and senile plaque (SP) densities, age of disease onset and durati on, and apolipoprotein E (ApoE) genotype. No age-related changes in ne urons occurred over four decades in 17 controls and regression analysi s of all AD cases showed no relationships between neuron, SP, and tau- immunoreactive NFT densities. Principal components analysis of neurons in layers III-Va and eigenvector projections showed five subgroups. T he subgroups were independent because each had a full range of disease durations and qualitatively different laminar patterns in degeneratio n suggested disease subtypes (ST). Cases with most severe neuron losse s (STSevere) had an early onset, most SP, and highest proportion of Ap oE epsilon 4 homozygotes. Changes in the distribution of NFT were simi lar over disease course in two subtypes and NFT did not account for mo st neurodegeneration. In STII-V with moderate neuron loss in most laye rs, cases with no NFT had a disease duration of 3.5 +/- 0.9 years (mea n +/- SEM), those with most in layers IIIc or Va had a duration of 7.3 +/- 1 years, and those with most in layers II-IIIab had a duration of 12.1 +/- 1 years. In STSevere, cases with highest NFT densities in la yers II-IIIab also were late stage. Finally, epsilon 4 homozygotes wer e most frequent in STSevere, but four statistical tests showed that th is risk is not directly involved in neurodegeneration. In conclusion, multivariate pattern recognition shows that AD is composed of independ ent neuropathological subtypes and NFT in area 23 do not account for m ost neuron losses. (C) 1998 Academic Press.