Fig. 1

Representation of cognitive aging in the presence of AD neuropathology in AD-patients and resilient individuals. Simplified overview of the AD neuropathological burden versus cognitive functioning during aging or disease progression. A Schematic of a resilient and AD brain with the neuropathological hallmarks of AD, neurofibrillary tangles (green arrows) and amyloid-beta plaques (brown arrows) and atrophic brain regions, as can be seen by the shrinkage of gyri and sulci and larger volume of the vessels, in AD. B Schematic of the progression of cognition and AD pathology over time. Plaques are present years before the onset of the disease and increase over time (brown line). The onset of phosphorylated tau (green line) follows and corresponds better with clinical progression in AD (red line). In later stages of the disease, comorbid pathology is often found in AD, such as TAR DNA-binding protein 43 (TPD-43) inclusions, α-synuclein (α-syn) or hippocampal sclerosis (purple line). It is hypothesized that resilient donors have a similar progression of AD pathology but are able to stay cognitively intact for a longer period (blue line). Multiple studies have also shown that in fact resilient donors are also to a certain extend resistant, as they have reduced amounts of AD pathology and comorbid pathology (dashed lines). Importantly, when low to intermediate amounts of AD pathology are present in the brain, it is difficult to differentiate resilient donors and those who would progress to dementia. Thus, in that timeframe it is difficult to assign resilient donors, which is here depicted as low likelihood of AD based on the amount of pathology