Neuropathologic assessment of dementia markers in identical and fraternal twins.

Twin studies are an incomparable source of investigation to shed light
on genetic and non-genetic components of neurodegenerative diseases, as
Alzheimer's disease (AD). Detailed clinicopathologic correlations using
twin longitudinal data and postmortem examinations are mostly missing.
We describe clinical and pathologic findings of 7 monozygotic (MZ) and
dizygotic (DZ) twin pairs. Our findings show good agreement between
clinical and pathologic diagnoses in the majority of the twin pairs,
with greater neuropathologic concordance in MZ than DZ twins. Greater
neuropathologic concordance was found for β-amyloid than tau pathology
within the pairs. ApoE4 was associated with higher β-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 AD pathology. These clinicopathologic
correlations of older identical and fraternal twins support the
relevance of genetic factors in AD, 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 AD.

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