Diagnostic accuracy of a global cognitive screen for Maori and non-Maori octogenarians.

INTRODUCTION: We assessed the sensitivity and specificity of the Modified Mini-Mental State Examination (3MS) in predicting dementia and cognitive impairment in Maori (indigenous people of New Zealand) and non-Maori octogenarians. METHODS: A subsample of participants from Life and Living in Advanced Age: a Cohort Study in New Zealand were recruited to determine the 3MS diagnostic accuracy compared with the reference standard. RESULTS: Seventy-three participants (44% Maori) completed the 3MS and reference standard assessments. The 3MS demonstrated strong diagnostic accuracy to detect dementia with areas under the curve of 0.87 for Maori and 0.9 for non-Maori. Our cutoffs displayed ethnic variability and are approximately 5 points greater than those commonly applied. Cognitive impairment yielded low accuracy, and discriminatory power was not established. DISCUSSION: Cutoffs that are not age or ethnically appropriate may compromise the accuracy of cognitive screens. Consequently, older age and indigeneity increase the risk of mislabeled cognitive status.

Cellular composition of human glial cultures from adult biopsy brain tissue.

Microglia and astrocytes play vital roles in normal human brain function and in neurological disorders. To study their physiological and pathological roles it is desirable to establish in vitro systems that are derived from the adult human brain. Although several groups have successfully cultured cells from the human brain, the composition of these cultures remains controversial. Using morphological criteria, immunocytochemical analysis and a BrdU incorporation assay we demonstrate the presence of poorly proliferative microglia and astrocytes in cultures derived from epilepsy biopsy tissue. In addition, we characterized a third cell type as fibronectin and prolyl 4-hydroxylase immunopositive fibroblast-like cells, which are highly proliferative and become the predominant cell type after successive sub-culturing. Therefore, although cultures from adult human brain tissue provide an excellent resource for studying human glial cells, careful consideration must be given to their cellular composition when performing studies using these methods.

TBP, a polyglutamine tract containing protein, accumulates in Alzheimer's disease.

Alzheimer's disease (AD) is characterised by extra cellular beta-amyloid (betaA) deposition, Tau-containing neurofibrillary tangles (NFTs) and progressive cortical atrophy. Abnormal protein accumulation is also a common feature of other late onset neurodegenerative diseases, including the heritable polyglutamine (polyQ) disorders such as Huntington disease (HD) and the spinocerebellar ataxias (SCAs). One of this family of disorders, SCA17, is caused by an expansion of a polymorphic polyQ repeat in TATA binding protein (TBP), an essential transcription factor. Surprisingly, the wild type TBP repeat length ranges from 25 to 42, and in Caucasian populations the most common allele is 38, a size large enough to cause HD if within the huntingtin protein. Wild type length TBP accumulates in HD and in at least some of the SCAs, and consequently we hypothesised that it may contribute to AD. Here we provide evidence that TBP accumulates in AD brain, localising to neurofibrillary tangle structures. A proportion of TBP present in AD brain is insoluble; a signature of the polyQ diseases. TBP is present differentially between patients and its amount and distribution is not directly proportional to that of Tau or beta-amyloid positive structures. We present this as evidence for the hypothesis that the accumulation or misfolding of this polyQ containing protein may be a contributing factor in Alzheimer's disease.