[123I]
Meta-iodobenzylguanidine (
MIBG) myocardial scintigraphy has been used to evaluate postganglionic cardiac sympathetic innervation in
heart diseases and some
neurological disorders. To see clinical usefulness of
MIBG myocardial scintigraphy to differentiate
Parkinson's disease (PD) and
dementia with Lewy bodies (DLB) from related
movement disorders and
Alzheimer disease (AD), we performed
MIBG myocardial scintigraphy in patients with these disorders. Cardiac uptake of
MIBG is specifically reduced in PD and DLB, and this imaging approach is a sensitive diagnostic tool that possibly differentiates PD and DLB from related
movement disorders and AD. To see pathological basis of the reduced cardiac uptake of
MIBG in
Lewy body disease, we immunohistochemically examined cardiac tissues from patients with PD, DLB, related
movement disorders and AD using
antibodies against
tyrosine hydroxylase (TH) and phosphorylated neurofilament (NF). Not only TH- but also NF-immunoreactive (ir) axons in the epicardial nerve fascicles were markedly decreased in
Lewy body disease, namely cardiac
sympathetic denervation, which accounts for the reduced cardiac uptake of
MIBG in
Lewy body disease. Patients with PD and DLB have Lewy bodies (LBs) in the nervous system, whereas patients with
multiple system atrophy (MSA),
progressive supranuclear palsy,
corticobasal degeneration, parkin-associated PD and AD have no LBs in the nervous system. Even in patients with MSA, cardiac
sympathetic denervation was associated with the presence of LBs. Therefore, cardiac
sympathetic denervation is closely related to the presence of LBs in a wide range of neurodegenerative processes. Taken together, we conclude that the reduced cardiac uptake of
MIBG is a potential
biomarker for the presence of LBs. Because
alpha-synuclein is one of the key molecules in the pathogenesis of PD, we further investigate how
alpha-synuclein aggregates are involved in degeneration of the cardiac sympathetic nerve in PD. We immunohistochemically examined cardiac tissues from patients with incidental
Lewy body disease (ILBD) and PD using
antibodies against TH and phosphorylated
alpha-synuclein. We found that (1)
alpha-synuclein aggregates in the epicardial nerve fascicles, namely the distal axons of the cardiac sympathetic nerve, were much more abundant in ILBD with preserved TH-ir axons than in ILBD with decreased TH-ir axons and PD; (2)
alpha-synuclein aggregates in the epicardial nerve fascicles were closely related to the disappearance of TH-ir axons; (3) in ILBD with preserved TH-ir axons,
alpha-synuclein aggregates were consistently more abundant in the epicardial nerve fascicles than in the paravertebral sympathetic ganglia (pSG); and (4) this distal-dominant accumulation of
alpha-synuclein aggregates was reversed in ILBD with decreased TH-ir axons and PD, which both showed decreased or depleted TH-ir axons but more abundant
alpha-synuclein aggregates in the pSG. These findings indicate that accumulation of
alpha-synuclein aggregates in the distal axons of the cardiac sympathetic nervous system precedes that of neuronal somata or neurites in the pSG and that heralds centripetal degeneration of the cardiac sympathetic nerve in PD. This chronological and dynamic relationship between
alpha-synuclein aggregates and distal-dominant degeneration of the cardiac sympathetic nervous system may represent the pathological mechanism underlying a common degenerative process in PD.