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 post-mortem examinations are mostly missing. We describe clinical and pathologic findings of seven 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.
The Brain Bank at Karolinska Institutet, KI Alzheimer Disease Research Center, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Stockholm, Sweden; Neuropathology Research, Biomedical Research Institute of New Jersey, BRInj, Cedar Knolls, NJ.
Diego
D
Iacono
Inga
I
Volkman
Inger
I
Nennesmo
Nancy L
NL
Pedersen
Laura
L
Fratiglioni
Boo
B
Johansson
David
D
Karlsson
Bengt
B
Winblad
Margaret
M
Gatz
D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism; D053327:Apolipoprotein E4 / Q000235:genetics; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D002561:Cerebrovascular Disorders / Q000473:pathology / Q000503:physiopathology; D015331:Cohort Studies; D003704:Dementia / Q000175:diagnosis / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D016631:Lewy Bodies / Q000473:pathology / Q000502:physiology; D008297:Male; D012042:Registries; D013548:Sweden; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; C054369:MAPT protein, human; D016875:tau Proteins
AD pathology; ApoE; aging; dementia; monozygotic and dizygotic twins; non-AD co-occurring brain pathologies