gms | German Medical Science

Alzheimer's disease (AD) is characterized by the presence of amyloid plaques (Ab) and neurofibrillary tangles (tau). In addition, concomitant protein depositions (in particular TDP-43 or a-synuclein) may be observed. An asymmetric distribution of neurodegeneration-related brain pathology has been described for plaques, tangles, granulovacuolar degeneration, neuronal loss and gliosis. In the present study, our aim was to comprehensively evaluate protein deposits of tau, pTDP-43, a-synuclein and Ab in paraffin-embedded tissue blocks of both hemispheres from patients with some degree of neurofibrillary degeneration. We evaluated 39 cases with pure AD-related pathology (n=20), additional brain infarction (n=4) or additional Lewy body disease (n=15). In 6 cases we observed significant difference between the two sides, resulting in a switch of stageing from transentorhinal to limbic in 5 cases, or from limbic to isocortical stage in one case. Further detailed evaluation of hippocampal subregions revealed side differences in tau pathology (n=14) as well as Ab deposits (n=8). Phosphorylated TDP-43 immunoreactivity was observed in 8 cases with side differences in all of them; in 2 cases one side showed complete lack of immunoreactivity. Thus, we extend the observations on the asymmetric distribution of AD pathology and show that a lateralized difference of Braak and Braak stages may be present in at least 15% of cases. In addition, 25% of cases with pTDP-43 pathology on one side may be negative on the other side. Our observations stress the importance of bilateral evaluation for diagnostic purposes and the need for correlative histology and biochemistry on corresponding material.