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Hans Braendgaard

Publications and source records attributed to Hans Braendgaard.

6 recordsLinked to original sources
PubMed2006

[Diagnostic imaging in dementia evaluation].

INTRODUCTION: The aim of the study was to evaluate the changes in diagnoses and treatment by structural scanning in dementia evaluation. MATERIAL AND METHODS: 336 elderly, consecutively evaluated patients from two university memory clinics (mean age 75 y, mean MMSE 21.7), were retrospectively diagnosed without and with inclusion of scan results. These results were compared to prospective data obtained from 137 patients scanned as part of a population based study (The Odense Study, mean age 78.5, mean MMSE 23.3). CT and MRI were performed in 93% and 7% of the patients, respectively. RESULTS: Potentially reversible structural pathology was found in 3.5% of the memory clinic patients, and in 2% of the population based patients. By applying international diagnostic criteria and treatment recommendations to the retrospective memory clinic data, it was found that adding a structural scan changed diagnoses and treatment in 37% and 33% of the patients, primarily due to identification of cerebrovascular disease (CVD) in patients with no clinical signs or symptoms of CVD. In comparison, the change in diagnosis found in the prospective population data was lower (15%). It was not possible to identify a group of patients that would not benefit from scanning. CONCLUSION: Our data support recent guidelines that suggest CT scan as a routine investigation in dementia evaluation.

Aged↗
PubMed2005

Familial Danish dementia: co-existence of Danish and Alzheimer amyloid subunits (ADan AND A{beta}) in the absence of compact plaques.

Familial Danish dementia is an early onset autosomal dominant neurodegenerative disorder linked to a genetic defect in the BRI2 gene and clinically characterized by dementia and ataxia. Cerebral amyloid and preamyloid deposits of two unrelated molecules (Danish amyloid (ADan) and beta-amyloid (Abeta)), the absence of compact plaques, and neurofibrillary degeneration indistinguishable from that observed in Alzheimer disease (AD) are the main neuropathological features of the disease. Biochemical analysis of extracted amyloid and preamyloid species indicates that as the solubility of the deposits decreases, the heterogeneity and complexity of the extracted peptides exponentially increase. Nonfibrillar deposits were mainly composed of intact ADan-(1-34) and its N-terminally modified (pyroglutamate) counterpart together with Abeta-(1-42) and Abeta-(4-42) in approximately 1:1 mixture. The post-translational modification, glutamate to pyroglutamate, was not present in soluble circulating ADan. In the amyloid fractions, ADan was heavily oligomerized and highly heterogeneous at the N and C terminus, and, when intact, its N terminus was post-translationally modified (pyroglutamate), whereas Abeta was mainly Abeta-(4-42). In all cases, the presence of Abeta-(X-40) was negligible, a surprising finding in view of the prevalence of Abeta40 in vascular deposits observed in sporadic and familial AD, Down syndrome, and normal aging. Whether the presence of the two amyloid subunits is imperative for the disease phenotype or just reflects a conformational mimicry remains to be elucidated; nonetheless, a specific interaction between ADan oligomers and Abeta molecules was demonstrated in vitro by ligand blot analysis using synthetic peptides. The absence of compact plaques in the presence of extensive neuro fibrillar degeneration strongly suggests that compact plaques, fundamental lesions for the diagnosis of AD, are not essential for the mechanism of dementia.

Adult↗
PubMed2003

Neurofilament inclusion body disease: a new proteinopathy?

We describe four cases of a new clinicopathological entity presenting with either a frontotemporal dementia or corticobasal degeneration syndrome with a mean age of onset of 45 years (range 41-50) characterized pathologically by deposition of neurofilament proteins. All four patients had a rapidly progressive course and have become mute and non-ambulatory, and three have died after mean illness duration of only 3 years (range 2 1/2 -4). Both structural (MRI) and functional (PET and SPECT) imaging demonstrated frontal and temporal lobe and basal ganglia involvement. Gross neuropathological examination in the three deceased patients (the fourth patient, still alive, was diagnosed by brain biopsy) revealed changes affecting predominantly the frontal and temporal cortices, basal ganglia and brainstem. There was superficial linear spongiosis affecting the frontal lobes in all three autopsied patients, and severe caudate atrophy was noted in two of them and demonstrated on MRI in the living patient. On routine staining, there were numerous intracytoplasmic inclusions, which ranged from eosinophilic to basophilic. Some had a clearly defined basophilic margin, while others were granular with a hyaline core. With modified Bielschowsky silver technique, a small number of the inclusions were intensely stained. Inclusions were not labelled with other silver stains. Immuno histochemistry revealed that the inclusions were immunoreactive with antibodies to neurofilament heavy and light chain subunits and to ubiquitin, but not with antibodies to tau and alpha-synuclein. These neurofilament- and ubiquitin-positive inclusions were widespread, specific to neurons and occasionally intranuclear. The frequency and distribution of the inclusions and the silver and immunohistochemical profiles in these four cases is novel and has not been described in detail before. We propose the term neurofilament inclusion body disease for this entity.

Adult↗
PubMed2002

Complement activation in chromosome 13 dementias. Similarities with Alzheimer's disease.

Chromosome 13 dementias, familial British dementia (FBD) and familial Danish dementia (FDD), are associated with neurodegeneration and cerebrovascular amyloidosis, with striking neuropathological similarities to Alzheimer's disease (AD). Despite the structural differences among the amyloid subunits (ABri in FBD, ADan in FDD, and Abeta in AD), these disorders are all characterized by the presence of neurofibrillary tangles and parenchymal and vascular amyloid deposits co-localizing with markers of glial activation, suggestive of local inflammation. Proteins of the complement system and their pro-inflammatory activation products are among the inflammation markers associated with AD lesions. Immunohistochemistry of FBD and FDD brain sections demonstrated the presence of complement activation components of the classical and alternative pathways as well as the neo-epitope of the membrane attack complex. Hemolytic experiments and enzyme-linked immunosorbent assays specific for the activation products iC3b, C4d, Bb, and C5b-9 indicated that ABri and ADan are able to fully activate the complement cascade at levels comparable to those generated by Abeta1-42. ABri and ADan specifically bound C1q with high affinity and formed stable complexes in physiological conditions. Activation proceeds approximately 70-75% through the classical pathway while only approximately 25-30% seems to occur through the alternative pathway. The data suggest that the chronic inflammatory response generated by the amyloid peptides in vivo might be a contributing factor for the pathogenesis of FBD and FDD and, in more general terms, to other neurodegenerative conditions.

Alzheimer Disease↗
PubMed2002

Familial Danish dementia: a novel form of cerebral amyloidosis associated with deposition of both amyloid-Dan and amyloid-beta.

Familial Danish dementia (FDD) is pathologically characterized by widespread cerebral amyloid angiopathy (CAA), parenchymal protein deposits, and neurofibrillary degeneration. FDD is associated with a mutation of the BRI2 gene located on chromosome 13. In FDD there is a decamer duplication, which abolishes the normal stop codon, resulting in an extended precursor protein and the release of an amyloidogenic fragment, ADan. The aim of this study was to describe the major neuropathological changes in FDD and to assess the distribution of ADan lesions, neurofibrillary pathology, glial, and microglial response using conventional techniques, immunohistochemistry, confocal microscopy, and immunoelectron microscopy. We showed that ADan is widely distributed in the central nervous system (CNS) in the leptomeninges, blood vessels, and parenchyma. A predominance of parenchymal pre-amyloid (non-fibrillary) lesions was found. Abeta was also present in a proportion of both vascular and parenchymal lesions. There was severe neurofibrillary pathology, and tau immunoblotting revealed a triplet electrophoretic migration pattern comparable with PHF-tau. FDD is a novel form of CNS amyloidosis with extensive neurofibrillary degeneration occurring with parenchymal, predominantly pre-amyloid rather than amyloid, deposition. These findings support the notion that parenchymal amyloid fibril formation is not a prerequisite for the development of neurofibrillary tangles. The significance of concurrent ADan and Abeta deposition in FDD is under further investigation.

Adult↗