Abstract
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Objectives Presynaptic cholinergic function may be differentially diminished in EOAD (disease onset at<65ys) and LOAD (onset at≥65ys), the most common form of all AD (95 %). To find out whether and to what extent α4β2*-nAChR binding is reduced in EOAD and LOAD, we investigated EOAD and LOAD which were matched for severity of mild to moderate dementia, disease duration, ApoE-status and education (p>0,2) using α4β2*-nAChR-specific 2-[18F]F-A-85380 (2FA)-PET.
Methods Non-smoking EOAD (n=11; 61±5ys; MMSE 22±6), LOAD (n=11; 74±5ys; MMSE: 19±7), matched for severity of dementia and two corresponding groups of age-matched healthy controls (HC1; n=18; 61±8ys and HC2; n=10; 70±6ys)(MMSE≥28) underwent 2FA-PET (ECAT Exact HR+). Parametric images of the binding potential (2FA-BP) using corpus callosum as reference region were determined (Logan plot; VOI-/SPM-analysis). Significance at p≤0.05 (SPM p≤0.001).
Results In EOAD, compared with HC1, 2FA-BP was significantly lower especially fronto-parieto-temporo-cingular, (para)hippocampal and thalamic (p<0.0001) and occipital (p<0.001). In LOAD, compared with HC2, 2FA-BP was significantly reduced especially temporo-hippocampal-(para)limbic (p<0.0001) and fronto-parieto-occipito-cingular (p<0.001). Directly compared with LOAD, in EOAD 2FA-BP was significantly lower parieto-temporo-occipital and higher temporal (left anterior)(p<0.001).
Conclusions We demonstrate for the first time that α4β2*-nAChR binding is differentially reduced in EOAD and LOAD, matched for severity of mild to moderate dementia. These regionally distinct reductions of α4β2*-nAChR binding in EOAD and LOAD resemble previously reported patterns of presynaptic cholinergic alterations. The more widespread α4β2*-nAChR reductions in EOAD, compared with LOAD, matched for severity of dementia, might predict a faster progression of disease