Figure 1.

Each case of idiopathic late-onset dementia is a unique mosaic of prototypical neuropathological landscapes. (a) Among individuals with idiopathic late-onset dementia (ILOD) there are variable amounts of proteopathic protein aggregates from absent/sparse (green) to moderate (orange) to extensive (red): amyloid β-peptide (Aβ), hyperphosphorylated Tau (pTau), TDP-43 (TDP43) and α-synuclein (αSyn). (b–e) Examples of neuropathological landscapes of four different patients with ILOD. (b) This patient exhibits robust Alzheimer’s disease pathology in the temporal, frontal and inferior parietal cortices with extensive Aβ and pTau pathologies. (c) This case is dominated by TDP-43 and p-Tau pathologies in the frontal and temporal lobes, with lesser amounts of TDP-43 in sensory and motor regions of the cerebral cortex, and moderate amounts of α-synuclein in the brainstem. (d) This patient exhibits prominent Lewy body (α-synuclein) pathology and moderate amounts of Aβ and pTau pathologies. (e) In some cases of ILOD there are low to moderate amounts of each of the four pathogenic proteins in the temporal, frontal and inferior parietal cortices, and extensive hippocampal sclerosis (HS).