Posterior cingulate cortex in familiar Alzheimer’s disease: A clinicopathological and brain imaging study

The degenerative process in Alzheimer´s disease (AD) follows a temporal and topographic pattern of early and accentuated involvement of temporal limbic, parietal and posterior cingulate cortices. We have studied a pedigree with four generations suffering from early onset AD linked to a presenilin-1 gene mutation. This family now contains 7 AD cases, neuropathologically confirmed in four cases of three generations. In all four cases the degeneration was most pronounced in the temporoparietal cortex, but also engaged central grey structures such as the claustrum, central thalamic and brain stem nuclei. There was a consistent and severe degeneration in posterior cingulate cortex in contrast to a compara¬tively spared anterior cingulum. Regional cerebral blood flow (rCBF) was studied repeated¬ly with 133-xenon inhalation and SPECT methods. The rCBF measurements showed the typical cortical pathology of AD with bilateral decreases in temporoparietal and posterior cingulate cortices, accentuating over time and spreading anteriorly. There was a very good correspondence between clinical, neuroimaging and neuropathological features. Our findings indicate that posterior cingulum is a major locus for functional and structural vulnerability in both familial and sporadic forms of AD, something that might be used for diagnostic purposes together with possible posterior cingulate symptomatology.