Sayoko Matsuno

Apolipoprotein E allele-dependent antioxidant activity in brains with Alzheimer's disease.

Article abstract Thiobarbituric acid–reactive substances (TBARS), an index of lipid peroxidation, were assayed in postmortem brain. Basal TBARS levels were increased and oxidative stimulation produced more TBARS in AD relative to control brains. In addition, apolipoprotein E isoforms showed differing antioxidant activities, with E2 > E3 > E4, suggesting that the lowest antioxidant activity of E4 could contribute to its association with AD.

Emergence of immunoreactivities for phosphorylated tau and amyloid-β protein in chronic stage of fluid percussion injury in rat brain

HEAD injury is one of the potential environmental factors in Alzheimers disease (AD). To study the chronic stage of concussive brain injury, histological analyses were performed 2–6 months after right lateral fluid percussion (FP) brain injury (3.6–4.8 atm) in rats. Six months after injury, numerous normal-looking neurons in the telencephalon and brain stem were immunoreactive with either antibody to phosphorylated tau or with four antibodies to β-amyloid protein. Neuronal counts in the cortices were gradually decreased after injury, up to 42% loss at 6 months after injury. These neuropathological changes suggest that this animal model could serve as a good animal model of neurodegenerative diseases such as AD.

Plasma levels of amyloid β 40 and 42 are independent from ApoE genotype and mental retardation in down syndrome

In Down syndrome (DS) brain an early, selective accumulation of amyloid beta (Abeta) peptides ending at residue 42 (Abeta42) occurs. Whether this event depends on an altered processing of amyloid beta precursor protein (APP) or on defective clearance is uncertain. To investigate this issue, we measured Abeta species 40 and 42 in plasma from 61 patients with DS, 77 age-matched normal controls, and 55 mentally retarded subjects without chromosomal abnormalities. The Abeta 40 and 42 plasma levels were then correlated with apolipoprotein E (apoE) genotypes in all groups of cases, and with I. Q. and Mini Mental Status Examination values in DS subjects. Both Abeta species were significantly elevated in DS compared to control groups, and the extent of their increase reflects that expected from APP gene overexpression. Plasma levels of Abeta 40 and 42 did not correlate with apoE genotypes in DS and control cases, and with the extent of mental retardation in DS subjects. The results indicate that accumulation and clearance of plasma and cerebral Abeta are regulated by different and independent factors.

Prednisolone (30–60 mg/day) for diseases other than AD decreases amyloid β-peptides in CSF

Abstract—The effect of corticosteroid on the concentration of amyloid &bgr;-peptide (A&bgr;) in human CSF obtained from 16 patients without dementia treated with prednisolone (≥30 mg daily) was studied. The concentrations of A&bgr;x–40 and A&bgr;x–42 in CSF decreased after treatment was started (p < 0.002). A moderate- or high-dose regimen of prednisolone decreases A&bgr; production or increases A&bgr; degradation in the human brain and deserves further study in AD.

Progressive encephalomyelitis with rigidity associated with anti-amphiphysin antibodies

Progressive encephalomyelitis with rigidity (PER) is a rare disorder of unknown aetiology, characterised by muscular rigidity, abnormal postures, painful muscle spasms, and myoclonus, and is caused by inflammation in the brainstem or spinal cord.1,2 We report a case of PER with positive anti-amphiphysin antibodies in the serum and CSF.3 This association has not been previously reported and raises the possibility that PER may have an autoimmune pathogenesis similar to that of stiff person syndrome (SPS).4 ### Clinical features A 37 year old female presented having had symptoms of PER for about three months. Spasms began with several minutes of paroxysmal painful muscle stiffness in the left upper limb, followed by pain and muscle spasms in the upper limbs, shoulders, neck, and back. These spasms were easily evoked by light touches, conversations, and by being startled. The patient remained bedridden and showed left dominant weakness of the limbs, with contractures in the upper limbs and difficulty in relaxing the muscles. She also developed abducent nerve palsy. Her deep tendon reflexes were absent and her plantar responses were both flexor. The serum antinuclear antibody was positive (1:160); …

Three-dimensional and fractal analyses of assemblies of amyloid β protein subtypes [Aβ40 and Aβ42(43)] in canine senile plaques

Abstract. The three-dimensional (3D) distribution of amyloid β protein (Aβ) subtypes [Aβ40 and Aβ42(43)] in canine senile plaques (SP) was observed using a confocal laser scanning microscope. In diffuse plaques (DP), Aβ42(43) alone was deposited as an uneven nebula-like assembly of fine granules. The border of the Aβ42(43) assembly was unclear and diffusely merged to the surrounding area. Mature plaques (MP), on the other hand, showed two patterns of Aβ deposition. In some MP, only Aβ40 was deposited as a defined assembly of very short fibrillary structures. Other MP consisted of both Aβ40 and Aβ42(43), and the deposition patterns of the two Aβ species were the same as those in single-positive plaques; fine granular with unclear margin for Aβ42(43), and short fibrillary structures for Aβ40. Additionally, we calculated the fractal dimensions (FD) of both Aβ40 and Aβ42(43) assemblies, and examined the serial change of FD in each SP. The FD of Aβ42(43)-positive DP ranged from 1.05 to 1.27, and those of Aβ40-positive MP ranged from 1.13 to 1.54 in single-positive plaques. In one double-positive MP, FD ranged from 1.02 to 1.36 for Aβ42(43) and from 1.01 to 1.51 for Aβ40. These results showed that the FD of canine Aβ40 assemblies was higher than that of Aβ42(43) assemblies, and the spatial changes of FD values for Aβ40 and Aβ42(43) in double-positive plaques were quite different. These morphological analyses clearly showed that canine DP and MP have completely different 3D structures, suggesting that their processes of formation are different.

Increased amyloid β protein in the skin of patients with amyotrophic lateral sclerosis

Abstract Distinct vascular and periadnexal immunoreactivity have been observed for amyloid b protein (Aβ) in skin from patients with amyotrophic lateral sclerosis (ALS). We used an enzyme-linked immunosorbent assay to make a more quantitative comparison of Aβ concentrations between ALS patients and controls. The insoluble fractions of skin samples from ALS patients contained significantly higher Aβ concentrations per milligram protein than those from controls. Various alterations in extracellular matrix components have been reported to occur in the skin of patients with ALS, and several matrix constituents have been shown to affect processing and aggregation of Aβ in human brain. Taking these previous findings together with those of the present study, our observations suggest that changes in extracellular matrix in skin of ALS patients may facilitate aggregation and deposition of Aβ.