A Histochemical Analysis of Neurofibrillary Tangles in Olfactory Epithelium, a Study Based on an Autopsy Case of Juvenile Alzheimer's Disease.

The pathological changes of Alzheimer's disease (AD) begin 10-20 years before clinical onset, and it is therefore desirable to identify effective methods for early diagnosis. The nasal mucosa is a target tissue for measuring AD-related biomarkers because the olfactory nerve is the only cranial nerve that is exposed to the external environment. We describe an autopsy case of rapidly advanced juvenile AD (JAD), focusing on the olfactory system. The formation of senile plaques, neurofibrillary tangles (NFTs), and neuropil threads was examined in the temporal cortex, hippocampus, olfactory bulb, and olfactory and respiratory epithelia in the bilateral olfactory clefts. Neurodegenerative changes in the olfactory and respiratory epithelia and the pathological deposition of amyloid ß42 (Aß42) and phosphorylated tau were also examined. As a result, senile plaques, NFTs, and neuropil threads were found in the temporal cortex, hippocampus, and olfactory bulb. NFTs were also found in the olfactory epithelium. Degenerated olfactory cells and their axons stained positive for phosphorylated tau. Supporting cells in the degenerated olfactory epithelium stained positive for Aß42. In conclusion, pathological biomarkers of AD were expressed in the degenerated olfactory epithelium of this JAD patient. This observation suggests that nasal samples may be useful for the diagnosis of AD.

Iron deposition in autopsied liver specimens from older patients receiving intravenous iron infusion.

BACKGROUND: Vitamins and minerals are routinely administered by total parenteral nutrition (TPN). However, in Japan, adjustments in iron dosage are difficult because blended mineral preparations are often used. It is therefore unclear whether the iron content is appropriate in cases of long-term TPN. The aim of the study was to assess the influence of iron administration by long-term TPN on iron deposition in post-mortem liver samples isolated from older deceased patients. METHODS: Liver tissues were collected from post-mortem autopsies of 187 patients over a period of 15 years. Samples were stained with Prussian blue and histologically evaluated from Grade 0-V by at least three different observers. Specimens with positive and negative iron staining were compared, and positive samples were grouped according to the level and distribution of the staining. Post-mortem blood obtained from the subclavian vein during autopsy was also analysed. Samples were collected for the measurement of unsaturated serum iron, serum iron, albumin, prealbumin, hepcidin, and IL-6 concentrations. RESULTS: Iron accumulation in the liver was significantly higher in male patients (p = 0.005) with a history of surgery (p = 0.044) or central vein administration of iron (p<0.001). Additionally, the duration of TPN in the iron-positive group was significantly longer than in the iron-negative group (p = 0.038). Serum analysis revealed that unsaturated serum iron was significantly higher in the iron-negative group and that ferritin and serum iron were significantly higher in the iron-positive group. No other statistically significant differences were observed between the two groups. CONCLUSIONS: Chronic intravenous administration of iron was associated with iron deposition in the liver, even when given the minimum recommended dosage. In long-term TPN patients, the iron dose should therefore be carefully considered.

Factors influencing hospital admission among patients with autopsy-confirmed dementia.

BACKGROUND: The symptoms of geriatric syndromes and the behavioural and psychological symptoms of dementia (BPSD), in addition to clinical conditions, are associated with hospital admission among dementia patients. However, the principal factors that necessitate hospital admission among dementia patients have not been fully elucidated. METHODS: We retrospectively reviewed the data in the medical and autopsy reports of patients who had been treated at a hospital in Toyohashi, Japan. Each patient had been hospitalized sometime between 2012 and 2016 and underwent a brain autopsy. Dementia and the subtypes of dementia were diagnosed neuropathologically. Information about patients' general backgrounds, clinical conditions at the time of admission, and the geriatric syndrome symptoms and BPSD before admission was collected; comparisons were then made between patients with and without dementia and among those with the different major subtypes of dementia. Then, the factors relating to hospital admission of dementia patients were comprehensively evaluated by using principle component analysis. RESULTS: Of the 128 eligible patients, 100 (78.1%) had dementia. In the comparison of patients with and without dementia, patients without dementia were younger at both admission (P = 0.034) and death (P = 0.003). Among the patients with dementia with Lewy bodies, delusions had a significantly high prevalence (P = 0.014). Principal component analysis identified nine components (disinhibition, irritability/lability, agitation/aggression, anxiety, delusions, sleep/night-time behaviour disorders, hallucinations, aberrant motor behaviour, and speech impairment) as the principal factors related to hospital admission among dementia patients. Thus, BPSD were identified as principal factors. CONCLUSIONS: Compared to other factors, BPSD are more likely to cause dementia patients to be admitted to hospital. The present results indicate that measures should be taken to ameliorate the difficulties associated with caring for patients with BPSD at home.

Enhanced vaccination effect against influenza by prebiotics in elderly patients receiving enteral nutrition.

AIM: We investigated the effect of prebiotics on the immunological response after influenza vaccination in enterally fed elderly individuals. The intervention group was given an enteral formula containing lactic acid bacteria-fermented milk products. In addition, two different types of other prebiotics, galacto-oligosaccharide and bifidogenic growth stimulator, were also given. The two prebiotics improved intestinal microbiota differently. In a control group, a standard formula without prebiotics was given. METHODS: An enteral formula with (intervention group [F]) or without (control group [C]) prebiotics was given through percutaneous endoscopic gastrostomy to elderly participants for 10 weeks. Influenza vaccine was inoculated at week 4. Nutritional and biochemical indices, intestinal micro bacteria and immunological indices were analyzed. RESULTS: The Bifidobacterium count in groups F and C at week 0 was 6.4 ± 1.9 and 6.6 ± 3.0 (log10 [count/g feces]), respectively. Although the count in group C decreased at week 10, the count in group F increased. The Bacteroides count in group F increased from 10.7 ± 0.9 to 11.4 ± 0.5, but decreased in group C from 11.2 ± 0.2 to 10.7 ± 0.4. Although the enhanced titers of H1N1, H3N2 and B antigens against the vaccine decreased thereafter in group C, these enhanced titers in group F could be maintained. CONCLUSION: Our findings suggest that prebiotics affect the intestinal microbiota and might maintain the antibody titers in elderly individuals.

Higher activity of peripheral blood angiotensin-converting enzyme is associated with later-onset of Alzheimer's disease.

According to the amyloid theory, the balance between amyloid-ß (Aß) production and degradation is key to the development of Alzheimer's disease (AD). Several enzymes including angiotensin-converting enzyme (ACE) have been reported as candidate enzymes involved in Aß degradation. We previously identified the relationship between ACE activity and AD. We present a comparison between AD and non-AD patients in the inpatient care unit of a geriatric hospital and have included the onset age and age at sampling in the comparison. We performed a colorimetric assay to determine ACE activity and a sandwich enzyme-linked immunosorbent assay (ELISA) to quantify blood plasma Aß 1-40 and 1-42 levels. Our 676 subjects, none of whom had received ACE inhibitor medication, included 147 AD patients. Clinical diagnoses were carried out to separate subjects into the AD and non-AD groups on the basis of the criteria of the International Classification of Diseases (ICD-10) and the Consortium to Establish a Registry for AD (CERAD). We found that the later the onset of AD, the higher the ACE activity, but there was no correlation between ACE activity and the Aß level in peripheral blood. In this report, we suggest that peripheral ACE activity may affect the age at AD onset.

Plasma levels of unactivated thrombin activatable fibrinolysis inhibitor (TAFI) are down-regulated in young adult women: analysis of a normal Japanese population.

Thrombin-activatable fibrinolysis inhibitor (TAFI) is an anaphylatoxin-inactivating enzyme generated by proteolytic cleavage of its zymogen, and is the same enzyme as that first designated by our group as procarboxypeptidase R (proCPR). TAFI in plasma is presumed to influence vascular disease in its role as a fibrinolysis inhibitor. The activity of TAFI is strongly influenced by genetic polymorphism, especially at amino acids Thr/Ala-147 and Thr/Ile-325. In this study, we analyzed 202 healthy controls who were not on any medication, had no unusual medical history and whose blood data were normal. In a previous report, we established an enzyme-linked immunosorbent assay (ELISA) specific for non-activated TAFI (proCPR), and investigated levels of unactivated TAFI as an estimate of anti-fibrinolytic capacity. In this study, we determined normal Japanese TAFI levels for each age, sex, and genetic polymorphism of Thr/Ala-147 and Thr/Ile-325, and also showed that the TAFI level in young adult women is lower than in aged women.