Contribution of asymmetric synapse loss to lateralizing clinical deficits in frontotemporal dementias

Background: Synapse loss has been found to be the major correlate of cognit ive decline in Alzheimer disease (AD), and prefrontal synapse loss has been found in patients with frontotemporal dementia (FTD). Objective: To see if our hypothesis that within each FTD case, regional syn apse loss would correlate with lateralizing neuropsychologic and neurobehav ioral deficits would be correct. Design: We analyzed synaptophysin as a marker for synapse loss in snap-froz en brain samples, using an enzyme-linked immunosorbent assay technique. Qua ntitative results were obtained by comparing patient data with a standard c urve made by analyzing serial dilutions of a recombinant synaptophysin prot ein fragment. A board-certified neuropsychologist and a board-certified neu rologist, both unaware of the synaptophysin results, determined areas of pr imary neuropsychologic and neurobehavioral dysfunction. Relationships betwe en areas of primary dysfunction and synapse loss were analyzed using the bi nomial test. Patients: Six cases of FTD, 28 cases of AD, and 16 nondemented control subj ects. Results: Five of 6 FTD cases had regional synaptophysins correlating with l ateralizing frontal or temporal deficits. Three of 6 correlated in 2 or mor e regions. Although our results were higher than that expected based on a p ure-chance mechanism (50% vs 34%), statistical significance was not attaine d. Conclusions: We found a trend for an association between synapse loss and l ateralizing neuropsychologic and neurobehavioral deficits in FTD. Studies i n larger numbers of FTD cases are planned with the goal of attaining statis tically significant conclusions.