KEGG pathway analysis of the DE proteins in P301S synapses showed significant enrichment in ‘metabolic pathways’ (containing mainly mitochondrial proteins such as Echs1, Maob and Atp8), ‘fatty acid degradation’ (for example Adh5, Hadha and Hadh), ‘peroxisome’ (for example Dhrs4, Ehhadh and Abcd1), ‘peroxisome proliferator-activated receptors (PPAR)’ signaling (for example Cpt1a and Cpt2), ‘Alzheimer’s disease’ (for example Adam10 and APOE) and ion homeostasis (for example Slc4a4 and Aqp4), especially prominent at 9 months (Fig. 2g). Here, HADHA is linked to early-onset autosomal dominant Alzheimer disease.