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We aimed to investigate the frequency of multiple system atrophy (MSA) in a large number of forensic autopsies and characterize the pathological appearance of preclinical MSA. We investigated a series of 1930 brains from forensic autopsies. In addition to performing immunohistochemistry for phosphorylated α-synuclein, the levels of 3 autonomic nervous system markers (catecholaminergic, serotonergic, and cholinergic) were used to assess the peripheral nerve (heart and superior cervical ganglion) and medulla oblongata. The results were compared to those of healthy control and Parkinson disease (PD) cases. Four cases (0.21%) were identified as having MSA. Cases 1-3 were symptomatic, and Case 4 was incipient; that is, although no neuronal loss was evident, the cerebellar dentate nucleus exhibited marked grumose degeneration. Immunohistochemistry revealed a marked reduction in autonomic nervous system marker levels expressed in the medulla; this reduction was more prominent in the 3 symptomatic MSA cases than in the PD case. The opposite occurred for the peripheral nerve. Case 4 exhibited mild cholinergic nerve reduction. Two cases showed possible significant pathological changes in the heart. Grumose degeneration, few oligodendroglial cytoplasmic inclusions without neuronal loss, and less reduction of autonomic nervous tissue were more prominent in the preclinical case than in symptomatic cases.

Here, we report a 74-year-old woman with a long history of schizophrenia but no clinical manifestation of dementia. Cause of death after autopsy was atherosclerotic heart disease. Although neuropathological investigation showed no significant brain atrophy, superficial microvacuolation with neuronal loss was restrictedly detected in the right anterior cingulate gyrus by microscopic examination. Pick bodies (PBs) positive for Bodian and Bielshowsky staining and 3-repeat-tau were detected in frontal and temporal lobes and limbic regions. Prevalence of PBs was most frequent in the right anterior cingulate gyrus and lateral base, followed by other neocortical regions of the frontal lobe, amygdala, and granular layer of the hippocampus. Although the number of glial inclusions was low, ramified astrocytes and various forms of astrocytes with AT8-positive inclusions were also found. Thus, the case may reflect preclinical or very early clinical Pick disease. Distribution of PBs does not necessarily have to be consistent with previously reported preclinical/early clinical Pick disease. These results show that tau pathology in the earlier stage of Pick disease may be heterogeneous, and the anterior cingulate gyrus may be initially affected in Pick disease. Neuropathological examination, including immunohistochemistry without case selection, is useful in identifying clinical and pathological manifestations of Pick disease.

We showed the results of pathological and genetic investigation for an autopsy case who was evaluated as longstanding Parkinson's disease (PD) in alive. Neuropathological investigation showed "pure nigropathy" without Lewy and tau pathology, and genetic analyses using next-generation sequencing detected novel TUBA4A nonsence mutation. Subsequent physiological study added to strength the hypothesis that the variant is pathogenic one. Present case showed TUBA4A is not only responsible gene for amyotrophic lateral sclerosis/frontotemporal dementia but also PD associated pure nigropathy. Also we found minimal but significant tau pathology high possibly associated with long-term deep brain stimulation in subthalamic nucleus.

Mouse testes contain several isoforms of cytoplasmic poly(A)-binding proteins (PABPCs), including ubiquitous PABPC1 and testis-specific PABPC2/PABPt. PABPC2 is characterized by its absence from translationally active polyribosomes and elongating spermatids. To elucidate the function of PABPC2 in spermatogenesis, we produced mutant mice lacking PABPC2. The PABPC2-null mice showed normal fertility. The processes of spermatogenesis and sperm migration in the testes and epididymides, respectively, were normal in the mutant mice. When the involvement of PABPC2 in translational regulation of haploid-specific mRNAs was examined, these mRNAs were correctly transcribed in round spermatids and translated in elongating spermatids. Moreover, immunoblot analysis revealed low abundance of PABPC2 relative to PABPC1 in spermatogenic cells. These results suggest that PABPC2 may be either functionally redundant with other PABPCs (including PABPC1) or largely dispensable for translational regulation during spermiogenesis.

The testis-specific cytoplasmic poly(A) polymerase PAPOLB/TPAP is essential for spermatogenesis. Although this enzyme is responsible for poly(A) tail extension of a subset of mRNAs in round spermatids, the stability and translational efficiency of these mRNAs are unaffected by the absence of PAPOLB. To clarify the functional importance of this enzyme’s adenylation activity, we produced PAPOLB-null mice expressing a polyadenylation-defective PAPOLB mutant (PAPOLBD114A), in which the catalytic Asp at residue 114 was mutated to Ala. Introducing PAPOLBD114A failed to rescue PAPOLB-null phenotypes, such as reduced expression of haploid-specific mRNAs, spermiogenesis arrest, and male infertility. These results suggest that PAPOLB regulates spermatogenesis through its adenylation activity.