Alzheimer’s disease (AD) diagnostic is based on clinical and biological criteria, and is dependent on impairment of the episodic memory together with a marker of the underlying pathophysiologic process. One of the earliest events in AD pathology in the brain is formation of Amyloid deposits in the extracellular space. One of the main subcellular sites of amyloid-β (Aβ) production from amyloid precursor protein (APP) processing is the endosomal compartment. Appearance of endosomal abnormalities precede the formation of amyloid deposits, in the brain areas affected by disease progression in AD. In the present work we first studied brain amyloid load in patients with posterior cortical atrophy using [11C]PiB ligand retention in positron emitting tomography (PET). In a second part we studied the endosomal compartment in peripheral cells (fibroblasts and mononuclear leucocytes, PBMC) from AD patients, and in lymphoblastoid cell lines (LCL) from Down’s syndrome (DS) individuals where a third copy of amyloid-precursor-protein-coding gene located on chromosome 21 is known to initiate early Alzheimer’s pathology in most DS individuals. Our work shows similar profiles in topography and intensity of [PiB] binding in AD and posterior cortical atrophy (PCA), confirming underlying AD pathology in atypical focal presentations of AD. Analysis of endosomes yielded a significant increase in the frequency of cells with large endosomes in all analyzed cell types, and mean endosome volume correlated to [PiB] binding in PBMC. This result indicates that modifications of the endosomal compartment are seen in the periphery of central nervous system and may represent diagnostic tool from blood.