mRNA Levels of BACE1 and its interacting proteins, RTN3 and PPIL2, correlate in human post mortem brain tissue

β-Site amyloid precursor protein cleaving enzyme (BACE1) is the rate-limiting enzyme for production of Aβ peptides, proposed to drive the pathological changes found in Alzheimer’s disease (AD). Reticulon 3 (RTN3) is a negative modulator of BACE1 (β-secretase) proteolytic activity, while peptidylprolyl isomerase (cyclophilin)-like 2 (PPIL2) positively regulated BACE1 gene expression in a cell-based assay. This study aimed to analyze RTN3 and PPIL2 mRNA levels in four brain regions from individuals with AD and controls. BACE1 mRNA had been previously quantified in the samples, as had glial fibrillary acidic protein (GFAP) and neuron-specific enolase (NSE), to track changing cell populations in the tissue. mRNA levels in the human post mortem brain tissue were assayed using quantitative real-time polymerase chain reaction (qPCR) and qbasePLUS, employing validated stably expressed reference genes. No differences in RTN3 or PPIL2 mRNA levels were found in individuals with AD, compared to controls. Both RTN3 and PPIL2 mRNA levels correlated significantly with BACE1 mRNA and all three showed similar disease stage-dependent changes with respect to NSE and GFAP. These findings indicated that the in vitro data demonstrating an effect of PPIL2 on BACE1 expression have functional relevance in vivo. Further research into BACE1-interacting proteins could provide a fruitful approach to the modulation of this protease and consequently Aβ production.

Service Provision for Children and Young People with Acquired Brain Injury; Practice Recommendations: – International Paediatric Brain Injury Society (IPBIS).

Background: Providing appropriate rehabilitation services for Acquired Brain Injury (ABI) in childhood presents a number of challenges for caregivers, health and education professionals and the young person as they develop.
Primary Objective: To record the challenges and possible creative solutions generated by an international group of professionals to address the needs of children with ABI.
Review of Information: Recommendations were generated from children’s special interest group meetings of the International Brain Injury Association (Turin Italy, 2001, Stockholm Sweden, 2003, Melbourne Australia, 2005, Lisbon Portugal, 2008) and through meetings of the International Paediatric Brain Injury Society (IPBIS), formed in 2009. Delegates participating in the workshops were representative of nations from around the world and included The Netherlands, New Zealand, Australia, UK, Finland, Germany, South Africa, USA, Canada, Sweden, Brazil and Italy.
Outcomes: The information presented is based on a retrospective review of those meetings and the summaries of the topics considered.

Wide-ranging alterations in the brain fatty acid complement of subjects with late Alzheimer's disease as detected by GC-MS

Disturbed lipid metabolism is a well-established feature of human Alzheimer's disease (AD). The present study used gas chromatography-mass spectrometry (GC-MS) analysis of fatty acid methyl esters (FAMES) to profile all detectable fatty acid (FA) species present in post-mortem neocortical tissue (Brodmann 7 region). Quantitative targeted analysis was undertaken from 29 subjects (n=15 age-matched controls; n=14 late-stage AD). GC-MS analysis of FAMES detected a total of 24 FAs and of these, 20 were fully quantifiable. The results showed significant and wide ranging elevations in AD brain FA concentrations. A total of 9 FAs were elevated in AD with cis-13,16-docosenoic acid increased most (170%; P=0.033). Intriguingly, docosahexanoic acid (DHA; C22:6) concentrations were elevated (47%; P=0.018) which conflicts with the findings of others (unaltered or decreased) in some brain regions after the onset of AD. Furthermore, our results appear to indicate that subject gender influences brain FA levels in AD subjects (but not in age-matched control subjects). Among AD subjects 7 FA species were significantly higher in males than in females. These preliminary findings pinpoint FA disturbances as potentially important in the pathology of AD. Further work is required to determine if such changes are influenced by disease severity or different types of dementia.

Traumatic brain injury (TBI) in a prison population: a systematic review

Objective: To systematically explore the literature surrounding TBI in adult prison populations. Method: Twenty six studies spanning six countries were included. All studies were published in peer reviewed journals and sampled adults from general prison populations (aged 18+). Results: Only seven studies employed valid and reliable measures of TBI. The presence of TBI related problems such as aggression, depression, substance abuse, psychiatric disorders, and neurocognitive deficits were evident within prisoner samples.