How to run a brain bank. A report from the Austro-German brain bank

The sophisticated analysis of and growing information on the human brain requires that acquisition, dissection, storage and distribution of rare material are managed in a professional way. In this publication we present the concept and practice of our brain bank. Both brain tissue and information are handled by standardized procedures and flow in parallel from pathology to neuropathology and neurochemistry. Data concerning brain material are updated with clinical information gained by standardized procedures

Increased levels of type VIII collagen in human brain tumours compared to normal brain tissue and non-neoplastic cerebral disorders.

The expression of type VIII collagen was examined in the normal and diseased human brain. Focal immunoreactivity was seen in histologically abnormal vessels of all four angiomas and 40 of 52 brain tumours (gliomas, meningiomas and schwannomas). An extended staining pattern, as well as a punctate distribution, was frequently observed in affected vessels. Staining was not apparent in nine normal brains and in 15 pathologic brains showing various cerebrovascular abnormalities, including Alzheimer's, Leigh's and Wernicke's diseases. Immunoblotting of glioblastomas revealed two bands at 56 kD and 67 kD which were also present at low levels in normal frontal cortex. The extracellular distribution of type VIII collagen was different from that of the other collagen types which have been described in brain and resembles patterns of expression described for certain tissues during mammalian embryogenesis (Kapoor et al., 1988). Our results provide additional evidence for the participation of type VIII collagen in some types of angiogenesis

Postmortem examination of vascular lesions in cognitive impairment: A survey among neuropathological services

Background and Purpose - A full appreciation of the presence of cerebral vascular lesions in cognitively impaired patients can be ultimately reached at the neuropathological level. However, there are no detailed guidelines regarding what neuropathologists should look for at autopsy in cases of suspected vascular dementia or vascular cognitive impairment. We aimed at surveying the postmortem neuropathological procedures used in different centers in examining brain lesions of presumable or possible vascular origin in cognitively impaired patients. Methods - Thirteen laboratories participated in the survey by filling in a semistructured questionnaire. We reviewed sampling and histology procedures in use and the neuropathological definitions of some of these lesions. Neuropathological criteria for the definition of a vascular origin of the dementing process were also surveyed. Results - A large variability across centers was observed in the procedures used for the neuropathological examination and the histology techniques. Heterogeneity existed also in the definition of commonly found lesions (eg, white matter alterations, small vessel disease), interpretation of whether or not the lesions were reputed to be of vascular origin, and consequently in the interpretation of the cause of cognitive decline. Conclusions - The appreciation of the presence of neuropathologically verified vascular lesions in cognitively impaired cases may be heavily influenced by the laboratory tools used and also by the heterogeneity of the criteria applied in different centers. Harmonization of neuropathological procedures is badly needed in the field of vascular dementia and vascular cognitive impairment to better understand the association between various vascular lesions and clinical symptoms such as cognitive impairment

Asymmetric Hypsarrhythmia: Clinical Electroencephalographic and Radiological Findings

Twenty-six children (16 boys and 10 girls) with hypsarrhythmia and infantile spasms (IS) were studied at the University of Michigan EEG Laboratory in a 4-year period. Six (2 boys, 4 girls), had asymmetric hypsarrhythmia with a preponderance of both slowing and epileptic form activity over one hemisphere. All 6 had the symptomatic form of IS, 4 with dysplastic conditions, 1 with porencephaly from a cerebral infarct, and 1 with hypoxic-ischemic encephalopathy. Five children had focal abnormalities on either physical examination or imaging studies. Four had the highest amplitude slowing and most epileptiform activity ipsilateral to the lesion, in 1, it was contralateral. Asymmetric hypsarrhythmia constituted 23% of cases with hypsarrhythmia examined at our EEG laboratory. The significant success in surgical therapy for some children with IS indicates the importance of identifying focal hemispheric abnormalities even if they are not apparent clinically. EEG may suggest focal changes not detected clinically or radiologically.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66439/1/j.1528-1157.1995.tb01663.x.pd

Magnetic resonance imaging brain atrophy assessment in primary age-related tauopathy (PART)

Alzheimer disease (AD) is a neurodegenerative disorder characterized pathologically by the accumulation of amyloid-beta (Aβ) plaques and tau neurofibrillary tangles (NFTs). Recently, primary age-related tauopathy (PART) has been described as a new anatomopathological disorder where NFTs are the main feature in the absence of neuritic plaques. However, since PART has mainly been studied in post-mortem patient brains, not much is known about the clinical or neuroimaging characteristics of PART. Here, we studied the clinical brain imaging characteristics of PART focusing on neuroanatomical vulnerability by applying a previously validated multiregion visual atrophy scale. We analysed 26 cases with confirmed PART with paired clinical magnetic resonance imaging (MRI) acquisitions. In this selected cohort we found that upon correcting for the effect of age, there is increased atrophy in the medial temporal region with increasing Braak staging (r = 0.3937, p = 0.0466). Upon controlling for Braak staging effect, predominantly two regions, anterior temporal (r = 0.3638, p = 0.0677) and medial temporal (r = 0.3836, p = 0.053), show a trend for increased atrophy with increasing age. Moreover, anterior temporal lobe atrophy was associated with decreased semantic memory/language (r = - 0.5823, p = 0.0056; and r = - 0.6371, p = 0.0019, respectively), as was medial temporal lobe atrophy (r = - 0.4445, p = 0.0435). Overall, these findings support that PART is associated with medial temporal lobe atrophy and predominantly affects semantic memory/language. These findings highlight that other factors associated with aging and beyond NFTs could be involved in PART pathophysiology.NACC database is funded by NIA/NIH Grant U01 AG016976. NACC data are contributed by the NIA-funded ADCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P30 AG062428–01 (PI James Leverenz, MD) P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P50 AG047266 (PI Todd Golde, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P30 AG062421–01 (PI Bradley Hyman, MD, PhD), P30 AG062422–01 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Thomas Wisniewski, MD), P30 AG013854 (PI Robert Vassar, PhD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P50 AG047366 (PI Victor Henderson, MD, MS), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P30 AG062429–01(PI James Brewer, MD, PhD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG053760 (PI Henry Paulson, MD, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P30 AG049638 (PI Suzanne Craft, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P30 AG062715–01 (PI Sanjay Asthana, MD, FRCP), P50 AG005681 (PI John Morris, MD), P50 AG047270 (PI Stephen Strittmatter, MD, PhD). NIH grants to JFC (R01AG054008, R01NS095252, R01AG062348, RF1AG060961), the Tau Consortium, and Alzheimer’s Association (NIRG- 469 15-363188

Tetraspanin (TSP-17) Protects Dopaminergic Neurons against 6-OHDA-Induced Neurodegeneration in <i>C. elegans</i>

Parkinson's disease (PD), the second most prevalent neurodegenerative disease after Alzheimer's disease, is linked to the gradual loss of dopaminergic neurons in the substantia nigra. Disease loci causing hereditary forms of PD are known, but most cases are attributable to a combination of genetic and environmental risk factors. Increased incidence of PD is associated with rural living and pesticide exposure, and dopaminergic neurodegeneration can be triggered by neurotoxins such as 6-hydroxydopamine (6-OHDA). In C. elegans, this drug is taken up by the presynaptic dopamine reuptake transporter (DAT-1) and causes selective death of the eight dopaminergic neurons of the adult hermaphrodite. Using a forward genetic approach to find genes that protect against 6-OHDA-mediated neurodegeneration, we identified tsp-17, which encodes a member of the tetraspanin family of membrane proteins. We show that TSP-17 is expressed in dopaminergic neurons and provide genetic, pharmacological and biochemical evidence that it inhibits DAT-1, thus leading to increased 6-OHDA uptake in tsp-17 loss-of-function mutants. TSP-17 also protects against toxicity conferred by excessive intracellular dopamine. We provide genetic and biochemical evidence that TSP-17 acts partly via the DOP-2 dopamine receptor to negatively regulate DAT-1. tsp-17 mutants also have subtle behavioral phenotypes, some of which are conferred by aberrant dopamine signaling. Incubating mutant worms in liquid medium leads to swimming-induced paralysis. In the L1 larval stage, this phenotype is linked to lethality and cannot be rescued by a dop-3 null mutant. In contrast, mild paralysis occurring in the L4 larval stage is suppressed by dop-3, suggesting defects in dopaminergic signaling. In summary, we show that TSP-17 protects against neurodegeneration and has a role in modulating behaviors linked to dopamine signaling

Spontaneous upper limb monoplegia secondary to probable cerebral amyloid angiopathy

Cerebral amyloid angiopathy is a clinicopathological disorder characterised by vascular amyloid deposition initially in leptomeningeal and neocortical vessels, and later affecting cortical and subcortical regions. The presence of amyloid within the walls of these vessels leads to a propensity for primary intracerebral haemorrhage. We report the unusual case of a 77-year-old female who presented to our emergency department with sudden onset isolated hypoaesthesia and right upper limb monoplegia. A CT scan demonstrated a peripheral acute haematoma involving the left perirolandic cortices. Subsequent magnetic resonance imaging demonstrated previous superficial haemorrhagic events. One week following discharge the patient re-attended with multiple short-lived episodes of aphasia and jerking of the right upper limb. Further imaging demonstrated oedematous changes around the previous haemorrhagic insult. Cerebral amyloid angiopathy is an overlooked cause of intracerebral haemorrhage; the isolated nature of the neurological deficit in this case illustrates the many guises in which it can present

Prefrontal cortex gyrification index in twins: an MRI study

Cortical development and folding seems to be under environmental as well as genetic control. The aim of our study was to estimate the genetic influence on gyrification and cortical volumes, comparing prefrontal gyrification index (GI) in monozygotic (MZ) and dizygotic (DZ) twin pairs, and unrelated pairs. Twenty-four subjects (6 pairs of MZ and 6 pairs of DZ twins) were included in this study. Prefrontal cortical folding (gyrification) was measured by an automated and manual version of the gyrification index (A-GI, M-GI) according to previously published protocols. MR-imaging was performed and 3 representative slices were selected from coronar MR-imaging scans. The volumes of the total brain, temporal lobes, prefrontal lobes, and cerebellum were analyzed, too. To evaluate similarity in GI, absolute differences in GI, and brain volumes as well as intraclass correlations of twin pairs were compared with regard to twin status. Finally, a control group of unrelated pairs was assembled from the first two study groups and analyzed. Compared to unrelated pairs, twin pairs exhibited more similarity concerning different brain volumes and a trend to more similarity concerning A-GI. MZ twins did not present more similarity concerning GI (automatically and manually measured) and volume measurements compared to DZ twins. Different factors, like intrauterine factors, postnatal development conditions, and especially environmental factors might account for the differences between related and unrelated pairs. The nonexistence of a pronounced similarity in MZ twins compared to DZ twins concerning prefrontal GI raises questions about the extent of genetic influence on GI

Post-mortem assessment in vascular dementia: advances and aspirations.

BACKGROUND: Cerebrovascular lesions are a frequent finding in the elderly population. However, the impact of these lesions on cognitive performance, the prevalence of vascular dementia, and the pathophysiology behind characteristic in vivo imaging findings are subject to controversy. Moreover, there are no standardised criteria for the neuropathological assessment of cerebrovascular disease or its related lesions in human post-mortem brains, and conventional histological techniques may indeed be insufficient to fully reflect the consequences of cerebrovascular disease. DISCUSSION: Here, we review and discuss both the neuropathological and in vivo imaging characteristics of cerebrovascular disease, prevalence rates of vascular dementia, and clinico-pathological correlations. We also discuss the frequent comorbidity of cerebrovascular pathology and Alzheimer's disease pathology, as well as the difficult and controversial issue of clinically differentiating between Alzheimer's disease, vascular dementia and mixed Alzheimer's disease/vascular dementia. Finally, we consider additional novel approaches to complement and enhance current post-mortem assessment of cerebral human tissue. CONCLUSION: Elucidation of the pathophysiology of cerebrovascular disease, clarification of characteristic findings of in vivo imaging and knowledge about the impact of combined pathologies are needed to improve the diagnostic accuracy of clinical diagnoses