Lewy body disease as a systemic disease Saito, Yuko; Murayama, Shigeo
Proceedings for Annual Meeting of The Japanese Pharmacological Society,
2022
Journal Article
Open access
Lewy body dementias (LBD) are classified into Parkinson's disease, Lewy body dementias, and pure autonomic failure according to the main lesion, and the lesions overlap in principle.On the other ...hand, we have clarified that the olfactory bulb / amygdala subtype secondary to Alzheimer's disease is characterized by the absence of Lewy bodies in the peripheral autonomic nervous system. In addition, multiple system atrophy and LBD-accumulated α-synuclein are stained with Gallyas silver stains, the former being positive and the latter being negative, and it is said that they differ in RT-QUIC and transmission to experimental animals. In LBD, cortical Lewy bodies and brainstem Lewy bodies have morphological differences with or without cores, and differences due to RT-QUIC have been reported. However, the differences in our previous Western blot studies did not confirm the differences observed in prion disease. There has been no report on the difference in the mechanism of α-synuclein aggregation in the Lewy body of the peripheral and central nervous system between primary and secondary LBD, and this is a topic for the future.
A Japanese male developed deafness, pyramidal signs and ataxia at age 50. A cerebrospinal fluid examination showed elevated levels of iron, transferrin and ferritin. Brain MRI showed atrophy of the ...cerebellum and pons as well as potential iron deposits on the surface of the brain. At autopsy, the brain weighed 1090 g and showed severe atrophy and necrosis of the cerebellum. No vascular malformation was observed. Extensive deposits of hemosiderin that were well stained with Berlin blue and ferritin immunohistochemistry were present at the surface and in the superficial layers of the cerebrum, brainstem, cerebellum and spinal cord. In these regions, numerous AT8 (p-Ï,,)-immunopositive deposits were present in neurons and glia. In addition, phosphorylated α-synuclein-immunopositive Lewy bodies and neurites were observed in the brainstem nuclei. In the present report, the authors derive the novel insight that superficial siderosis is a distinctive entity associated with tauopathy and synucleinopathy.
Abstract only
Levodopa‐responsive Parkinsonism may be dominant phenotype of patients with SCA2. In general, they have a shorter abnormal expansion of CAG repeats (less than 39) in
ATXN2
gene. The aim ...is to elucidate neuropathologic basis of this variant SCA2 from different Japanese families and give a new perspective on pathogenesis of SCA2 with Parkinsonism.
Case 1
: He was diagnosed as having Parkinson's disease at age 50. At age 65, he showed cerebellar ataxia and slow eye movement.
Case 2
: He developed unstable gait at age 40. In addition to the ataxia, he had rigidity, bradykinesia, stooped posture and freezing gait. Genetic analyses of
ATXN2
showed an expanded CAG repeat with 22/38 (case 1) and 22/37 (case 2).
Neuropathology
: There is an atrophy of the pons and cerebellum. The most striking finding was the presence of α‐synuclein immunoreactive Lewy bodies (LBs) and neuritis (LNs) in the locus coeruleus, dorsal motor nucleus of vagus, basal nucleus of Meynert and amygdala. LBs and LNs were also seen in the substantia nigra. The distribution of Lewy pathology was consistent with stage 2 (case 1) and stage 3 (case 2) according to Braak's criteria. The 1C2 antibody depicted intranuclear immunopositive deposits in the various regions. In addition, α‐synuclein deposits were not seen in SCA2 cases without Parkinsonism.
We conclude that α‐synucleinopathy is vital pathologic alterations of SCA2 with Parkinsonism. JSPS 19500311
Alteration of glycoprotein glycans often changes various properties of the target glycoprotein and contributes to a wide variety of diseases. Here, we focused on the N-glycans of amyloid precursor ...protein whose cleaved fragment, b-amyloid, is thought to cause much of the pathology of Alzheimer's disease (AD). We previously determined the N-glycan structures of normal and mutant amyloid precursor proteins (the Swedish type and the London type). In comparison with normal amyloid precursor protein, mutant amyloid precursor proteins had higher contents of bisecting GlcNAc residues. Because N-acetylglucosaminyltransferase III (GnT-III) is the glycosyltransferase responsible for synthesizing a bisecting GlcNAc residue, the current report measured GnT-III mRNA expression levels in the brains of AD patients. Interestingly, GnT-III mRNA expression was increased in AD brains. Furthermore, b-amyloid treatment increased GnT-III mRNA expression in Neuro2a mouse neuroblastoma cells. We then examined the influence of bisecting GlcNAc on the production of b-amyloid. Both b-amyloid 40 and b-amyloid 42 were significantly decreased in GnT-III-transfected cells. When secretase activities were analyzed in GnT-III transfectant cells, a-secretase activity was increased. Taken together, these results suggest that upregulation of GnT-III in AD brains may represent an adaptive response to protect them from additional b-amyloid production.
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