Lewy body pathology in late-onset familial Alzheimer's disease: a clinicopathological case series.
BACKGROUND
Lewy body pathology (LBP) is a common finding in Alzheimer's disease (AD), but the pathophysiology for this coexistent pathology remains unclear.


METHODS
We ascertained late-onset dementia (mean age > 60 years old) families with at least 3 autopsies. We then conducted systematic alpha-synuclein (SNCA) immunostaining to determine the frequency and distribution of LBP in families with late-onset AD.


RESULTS
All 32 subjects met NIA-Reagan neuropathological criteria for "high likelihood" of having AD. Hematoxylin and eosin staining detected LBP in the substantia nigra (SN) in 8 (25%) individuals. SNCA immunostaining detected LBP in 21 individuals (66%). While all subjects with SN LBP had co-existent amygdala LBP, many (9/21, 43%) of the cases with amygdala LBP did not have coexistent SN LBP (McNemar's chi-square test, p=0.008). Each family had at least two cases with LBP, but no family had LBP in all autopsied cases.


CONCLUSIONS
Presence of significant AD pathology in one family member was highly predictive of similar pathology in other family members. However, despite the use of more sensitive SNCA immunohistochemistry, the presence of LBP was variable within all 7 families. Consistent with previous studies in sporadic and familial AD, the amygdala appeared to be the most vulnerable region for LBP in AD. Additional clinical, neuropathologic, and genetic studies are necessary to determine the clinical and pathological significance of LBP in AD.
Tsuang
Debby W
DW
Mental Illness Research, Education, and Clinical Centers, Veteran Affairs Puget Sound Health Care System, Seattle, WA 98108, USA. dwt1@u.washington.edu
Riekse
Robert G
RG
Purganan
Kristina M
KM
David
Andrew C
AC
Montine
Thomas J
TJ
Schellenberg
Gerard D
GD
Steinbart
Ellen J
EJ
Petrie
Eric C
EC
Bird
Thomas D
TD
Leverenz
James B
JB
D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D000679:Amygdala / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D001921:Brain / Q000473:pathology; D005190:Family; D005260:Female; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D016631:Lewy Bodies / Q000235:genetics / Q000473:pathology*; D008297:Male; D013378:Substantia Nigra / Q000473:pathology; D051844:alpha-Synuclein / Q000378:metabolism
D001057:Apolipoproteins E; D051844:alpha-Synuclein