Description:
<jats:title>Abstract</jats:title><jats:p>Twin studies are an incomparable source of investigation to shed light on genetic and non‐genetic components of neurodegenerative diseases, as Alzheimer's disease (<jats:styled-content style="fixed-case">AD</jats:styled-content>). Detailed clinicopathologic correlations using twin longitudinal data and post‐mortem examinations are mostly missing. We describe clinical and pathologic findings of seven monozygotic (<jats:styled-content style="fixed-case">MZ</jats:styled-content>) and dizygotic (<jats:styled-content style="fixed-case">DZ</jats:styled-content>) twin pairs. Our findings show good agreement between clinical and pathologic diagnoses in the majority of the twin pairs, with greater neuropathologic concordance in <jats:styled-content style="fixed-case">MZ</jats:styled-content> than <jats:styled-content style="fixed-case">DZ</jats:styled-content> twins. Greater neuropathologic concordance was found for <jats:styled-content style="fixed-case">β</jats:styled-content>‐amyloid than tau pathology within the pairs. <jats:styled-content style="fixed-case">ApoE</jats:styled-content>4 was associated with higher <jats:styled-content style="fixed-case">β</jats:styled-content>‐amyloid and earlier dementia onset, and importantly, higher frequency of other co‐occurring brain pathologies, regardless of the zygosity. Dementia onset, dementia duration, difference between twins in age at dementia onset and at death, did not correlate with <jats:styled-content style="fixed-case">AD</jats:styled-content> pathology. These clinicopathologic correlations of older identical and fraternal twins support the relevance of genetic factors in <jats:styled-content style="fixed-case">AD</jats:styled-content>, but not their sufficiency to determine the pathology, and consequently the disease, even in monozygotic twins. It is the interaction among genetic and non‐genetic risks which plays a major role in influencing, or probably determining, the degeneration of those brain circuits associated with pathology and cognitive deficits in <jats:styled-content style="fixed-case">AD</jats:styled-content>.</jats:p>