Amyloid Beta Annular Protofibrils in Cell Processes and Synapses Accumulate with Aging and Alzheimer-Associated Genetic Modification

Amyloid β (Aβ) annular protofibrils (APFs) have been described where the structure is related to that of β barrel pore-forming bacterial toxins and exhibits cellular toxicity. To investigate the relationship of Aβ APFs to disease and their ultrastructural localization in brain tissue, we conducted a pre-embedding immunoelectron microscopic study using anti-annular protofibril antiserum. We examined brain tissues of young- and old-aged amyloid precursor protein transgenic mice (APP23), neprilysin knockout APP23 mice, and nontransgenic littermates. αAPF-immunoreactions tended to be found (1) on plasma membranes and vesicles inside of cell processes, but not on amyloid fibrils, (2) with higher density due to aging, APP transgene, and neprilysin deficiency, and (3) with higher positive rate at synaptic compartments in aged APP23, especially in neprilysin knockout APP23 mice. These findings imply that APFs are distinct from amyloid fibrils, interact with biological membranes, and might be related to synaptic dysfunction in Alzheimer model mouse brains

Selective vulnerability of different types of commissural neurons for amyloid β-protein-induced neurodegeneration in APP23 mice correlates with dendritic tree morphology

The amyloid β-protein (Aβ) is the main component of Alzheimer's disease-related senile plaques. Although Aβ is associated with the development of Alzheimer's disease, it has not been shown which forms of Aβ induce neurodegeneration in vivo and which types of neurons are vulnerable. To address these questions, we implanted DiI crystals into the left frontocentral cortex of APP23 transgenic mice overexpressing mutant human APP (amyloid precursor protein gene) and of littermate controls. Traced commissural neurons in layer III of the right frontocentral cortex were quantified in 3-, 5-, 11- and 15-month-old mice. Three different types of commissural neurons were traced. At 3 months of age no differences in the number of labelled commissural neurons were seen in APP23 mice compared with wild-type mice. A selective reduction of the heavily ramified type of neurons was observed in APP23 mice compared with wild-type animals at 5, 11 and 15 months of age, starting when the first Aβ-deposits occurred in the frontocentral cortex at 5 months. The other two types of commissural neurons did not show alterations at 5 and 11 months. At 15 months, the number of traced sparsely ramified pyramidal neurons was reduced in addition to that of the heavily ramified neurons in APP23 mice compared with wild-type mice. At this time Aβ-deposits were seen in the neo- and allocortex as well as in the basal ganglia and the thalamus. In summary, our results show that Aβ induces progressive degeneration of distinct types of commissural neurons. Degeneration of the most vulnerable neurons starts in parallel with the occurrence of the first fibrillar Aβ-deposits in the neocortex, that is, with the detection of aggregated Aβ. The involvement of additional neuronal subpopulations is associated with the expansion of Aβ-deposition into further brain regions. The vulnerability of different types of neurons to Aβ, thereby, is presumably related to the complexity of their dendritic morpholog

Yamaguchi Facial Expression-Making Task in Alzheimer’s Disease: A Novel and Enjoyable Make-a-Face Game

Background: To assess the ability to make emotional facial expressions, we newly developed the Yamaguchi facial expression-making task (Y-FEMT). Method: We recruited 20 normal controls and 61 outpatients: 10 with amnestic mild cognitive impairment (aMCI), 34 with mild Alzheimer’s disease (AD), and 17 with moderate AD. In the Y-FEMT, smile and anger expressions were made by arranging face parts. We examined the relationship between each Y-FEMT score and the Mini-Mental State Examination (MMSE) score or overlapping figure identification test (Fig-test). Results: The Total score (0–20) was nearly achieved in controls (18.9 ± 1.4) and declined with AD progression (aMCI 17.2 ± 2.4, mild AD 15.7 ± 2.6, moderate AD 12.3 ± 2.7). The Anger score (0–10) was significantly lower than the Smile score (0–10) in mild and moderate AD (p = 0.007 and p = 0.006, respectively). The Structure score (0–6 each) correlated well with both the MMSE score (r = 0.44, p Conclusion: The Y-FEMT pleasantly assessed the ability to make emotional facial expressions without special equipment. Furthermore, the Y-FEMT may provide helpful clues for caregivers to achieve good communication with AD patients for better care

Evaluation of Anosognosia in Alzheimer's Disease Using the Symptoms of Early Dementia-11 Questionnaire (SED-11Q)

Aims: The objective is to propose a brief method to evaluate anosognosia in Alzheimer's disease (AD) using the Symptoms of Early Dementia-11 Questionnaire (SED-11Q), a short informant-based screening questionnaire for identifying dementia. Methods: The participants were 107 elderly individuals: 13 with a Clinical Dementia Rating (CDR) of 0.5, 73 with mild AD of CDR 1, and 21 with moderate AD of CDR 2. The patients and caregivers answered the SED-11Q independently, and the degree of discrepancy indicated the severity of anosognosia. Results: The scores were as follows: caregiver scores were 2.46 ± 1.85 (mean ± SD) in CDR 0.5, 6.36 ± 3.02 in CDR 1, and 9.00 ± 1.14 in CDR 2; patient scores were 2.00 ± 1.78, 2.55 ± 2.33, and 1.33 ± 2.46, respectively. Discrepancy was 0.46 ± 1.61, 3.81 ± 3.95, and 7.67 ± 2.87, respectively, and the caregiver assessments were significantly higher than the patient assessments in CDR 1 and CDR 2 (p Conclusion: The SED-11Q serves a dual purpose: caregiver assessment is useful for the screening of dementia, and any discrepancy between the patient and the caregiver assessment is considered as an indication of the severity of anosognosia; this can be informative for caregivers and essential for successful care

Symptoms of Early Dementia-11 Questionnaire (SED-11Q): A Brief Informant-Operated Screening for Dementia

The aim of this study was to develop a brief informant-based questionnaire, namely the Symptoms of Early Dementia-11 Questionnaire (SED-11Q), for the screening of early dementia. 459 elderly individuals participated, including 39 with mild cognitive impairment in the Clinical Dementia Rating scale (CDR) 0.5, 233 with mild dementia in CDR 1, 106 with moderate dementia in CDR 2, and 81 normal controls in CDR 0. Informants were required to fill out a 13-item questionnaire. Two items were excluded after analyzing sensitivities and specificities. The final version of the SED-11Q assesses memory, daily functioning, social communication, and personality changes. Receiver operator characteristic curves assessed the utility to discriminate between CDR 0 (no dementia) and CDR 1 (mild dementia). The statistically optimal cutoff value of 2/3, which indicated a sensitivity of 0.84 and a specificity of 0.90, can be applied in the clinical setting. In the community setting, a cutoff value of 3/4, which indicated a sensitivity of 0.76 and a specificity of 0.96, is recommended to avoid false positives. The SED-11Q reliably differentiated nondemented from demented individuals when completed by an informant, and thus is practical as a rapid screening tool in general practice, as well as in the community setting, to decide whether to seek further diagnostic confirmation

Effect of group activities on health promotion for the community-dwelling elderly

Abstract Objective: In Japan, the Integrated Community Care System aims to support residents to live as independently as possible at home. Koreisya-Kyoshitsu and Fureaiikiiki salons are two types of group activities for community-dwelling elderly. We investigated effective ways of conducting such activities. Methods: We analyzed 96 subjects from 8 salons and 354 subjects from 10 Koreisya-Kyoshitsu. Self-completed questionnaires included the following: attributes, the Motor Fitness Scale (MFS), revised Philadelphia Geriatric Center Morale Scale (PGCMS), Measurement of Psychological Independence (MPI), instrumental activities of daily living (IADL), and self-rated health status (SRH). Followup assessment was conducted 6 months later. Representatives from 8 salons and staff members from 10 Koreisya-Kyoshitsu answered an additional questionnaire on management. Results: In Koreisya-Kyoshitsu, physical performance (MFS) (p = 0.007) and subjective well-being (PGCMS) (p = 0.001) improved significantly, whereas psychological independence (MPI) deteriorated significantly (p = 0.015). The MFS scores significantly improved in the sub-group with a high number of sessions (7 or more) (p = 0.043), as well as in the non-volunteer sub-group (p = 0.004). The PGCMS scores significantly improved in the subgroup with a high number of sessions (p < 0.001). The MPI scores significantly deteriorated in the sub-group with a low frequency of sessions (6 or less) and in the non-volunteer sub-group (p = 0.013 and p = 0.010, respectively). In salons, the frequency of going out decreased significantly (p = 0.049). Functional status (IADL) significantly improved in the "twice or more a month" sub-group (p = 0.046), whereas it significantly deteriorated in the "once a month" sub-group (p = 0.004). The proportion of volunteers/organizers in Koreisya-Kyoshitsu (23.4%) was significantly lower than that in salons (39.6%). Conclusion: The frequency (number) of sessions, but not the volunteer/non-volunteer attribute, was a key factor in obtaining the health promotion effects of group activities in both Koreisya-Kyoshitsu and salons

Formic Acid Pretreatment Selectively Abolishes Argyrophilia of Senile Plaques in the Brain of the Alzheimer-type Dementia

We studied the effect of formic acid pretreatment on silver stains and βprotein immunostain on brain tissue samples from patients with the Alzheimer-type dementia (AID). The argyrophilia of the amyloid component of senile plaques (SP), which could be visualized by modified Bielschowsky and periodic acid-methenamine silver (PAM) stains, was not visible when the specimens were pretreated with formic acid. In contrast, the pretreatment highly enhanced the immunoreactivity of this component with βprotein antiserum. Our findings suggest that formic acid pretreatment selectively abolishes the argyrophilia of the amyloid component of SP