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Braak Stage (braak + stage)
Selected AbstractsHereditary cerebral hemorrhage with amyloidosis-Dutch typeNEUROPATHOLOGY, Issue 4 2005Marion Maat-Schieman The amyloid ,-protein (A,) E22Q mutation of the rare disorder hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D) causes severe cerebral amyloid angiopathy (CAA) with hemorrhagic strokes of mid-life onset and dementia. The mutation does not affect total A, production but may alter the A,1,42:A,1,40 ratio, and affect the proteolytic degradation of A, and its transport across the blood,brain barrier. A, E22Q aggregates faster into more stable amyloid-like fibrils than wild-type A,. Non-fibrillar A,(x-42) deposits precede the appearance of fibrils and the deposition of A,(x-40) in the vascular basement membrane. CAA severity tends to increase with age but may vary greatly among patients of comparable ages. Lumenal narrowing of affected blood vessels, leukoencephalopathy, CAA-associated vasculopathies, and perivascular astrocytosis, microgliosis, and neuritic degeneration complicate the development of HCHWA-D CAA. Parenchymal A, deposition is also enhanced in the HCHWA-D brain with non-fibrillar membrane-bound A,(x-42) deposits evolving into relatively fibrillar diffuse plaques variously associated with reactive astrocytes, activated microglia, and degenerating neurites. Plaque density tends ,to ,decrease ,with ,age. ,Neurofibrillary ,degeneration is absent or limited. HCHWA-D dementia is associated with CAA severity independently of Braak stage, age, and plaque density. Particularly, microaneurysms may contribute to the development of (small) hemorrhages/infarcts and the latter to cognitive decline in affected subjects. However, the relative importance of cerebral hemorrhages/infarcts, white matter damage and/or other CAA- or A,-related factors for cognitive deterioration in HCHWA-D remains to be determined. [source] Ballooned neurones in the limbic lobe are associated with Alzheimer type pathology and lack diagnostic specificityNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 6 2004Y. Fujino Ballooned neurones (BNs) are one of the pathological hallmarks of several neurodegenerative diseases, including Pick's disease, corticobasal degeneration and argyrophilic grain disease (AGD). They have also been described in Alzheimer disease (AD), but the frequency of BNs in AD has not been systematically addressed. In the present study, immunohistochemistry for ,B-crystallin was used as a sensitive method to detect BNs to determine the frequency of BNs in the limbic lobe in AD. At least a few BNs were detected in the limbic lobe of virtually all AD cases, and their density correlated with Braak stage, as well as the density of neurofibrillary tangles and senile plaques in the limbic lobe. The density of BN tended to be greater in AD cases with concurrent AGD than in pure AD. Given the high prevalence of AD in brain banks for neurodegenerative disease and the frequent presence of BNs in these areas with ,B-crystallin immunohistochemistry, the present findings further indicate that BNs confined to the limbic lobe lack specificity in diagnostic neuropathology. [source] A critical evaluation of the Braak staging scheme for Parkinson's disease,ANNALS OF NEUROLOGY, Issue 5 2008Robert E. Burke MD Braak and colleagues have proposed that, within the central nervous system, Parkinson's disease (PD) begins as a synucleinopathy in nondopaminergic structures of the lower brainstem or in the olfactory bulb. The brainstem synucleinopathy is postulated to progress rostrally to affect the substantia nigra and cause parkinsonism at a later stage of the disease. In the context of a diagnosis of PD, made from current clinical criteria, the pattern of lower brainstem involvement accompanying mesencephalic synucleinopathy is often observed. However, outside of that context, the patterns of synucleinopathy that Braak described are often not observed, particularly in dementia with Lewy bodies and when synucleinopathy occurs in the absence of neurological manifestations. The concept that lower brainstem synucleinopathy represents "early PD" rests on the supposition that it has a substantial likelihood of progressing within the human lifetime to involve the mesencephalon, and thereby cause the substantia nigra pathology and clinical parkinsonism that have heretofore defined the disease. However, the predictive validity of this concept is doubtful, based on numerous observations made in populations of aged individuals who, despite the absence of neurological signs, have brain synucleinopathy ranging up to Braak stages 4 to 6 at postmortem. Furthermore, there is no relation between Braak stage and the clinical severity of PD. We conclude that the relation between patterns of abnormal synuclein immunostaining in the human brain and the disease entity now recognized as PD remains to be determined. Ann Neurol 2008;64:485,491 [source] Oligomeric A, in Alzheimer's Disease: Relationship to Plaque and Tangle Pathology, APOE Genotype and Cerebral Amyloid AngiopathyBRAIN PATHOLOGY, Issue 2 2010Zoë Van Helmond Abstract Despite accumulating evidence of a central role for oligomeric amyloid , (A,) in the pathogenesis of Alzheimer's Disease (AD), there is scant information on the relationship between the levels and distribution of oligomeric A, and those of other neurodegenerative abnormalities in AD. In the present study, we have found oligomeric A, to be associated with both diffuse and neuritic plaques (mostly co-localized with A,1,42) and with cerebrovascular deposits of A, in paraffin sections of formalin-fixed human brain tissue. The amount of oligomeric A, that was labeled in the sections correlated with total A, plaque load, but not phospho-tau load, cerebral amyloid angiopathy (CAA) severity or APOE genotype. Although soluble, oligomeric and insoluble A, levels were all significantly increased in AD brain homogenates, case-to-case variation and overlap between AD and controls were considerable. Over the age-range studied (43,98 years), the levels of soluble A,, oligomeric A,42, oligomeric A,40 and insoluble A, did not vary significantly with age. Oligomeric A,1,42 and insoluble A, levels were significantly higher in women. Overall, the level of insoluble A,, but neither oligomeric nor soluble A,, was associated with Braak stage, CAA severity and APOE,4 frequency, raising questions as to the role of soluble and oligomeric A, in the progression of AD. [source] Are dysautonomic and sensory symptoms present in early Parkinson's disease?ACTA NEUROLOGICA SCANDINAVICA, Issue 2010O.-B. Tysnes Tysnes O-B, Müller B, Larsen JP. Are dysautonomic and sensory symptoms present in early Parkinson's disease? Acta Neurol Scand: 2010: 122 (Suppl. 190): 72,77. © 2010 John Wiley & Sons A/S. Parkinson's disease (PD) occurs with an annual incidence of 13/100.000, is slightly more frequent in men and is characterized by the motor symptoms tremor, rigidity, bradykinesia and postural instability. In addition, non-motor symptoms have been increasingly connected to the disease although already described in James Parkinson's ,Essay on the shaking palsy' from 1817. The motor symptoms in PD are related to the degeneration of dopaminergic cells in the substantia nigra (SN). These symptoms respond well to dopaminergic substitution. It is much more unclear whether non-motor symptoms like dysautonomia, insomnia, day-time sleepiness, fatigue, pain and neuropsychiatric symptoms respond to levodopa. Autonomic symptoms include dizziness because of orthostatic hypotension, constipation, nausea, voiding symptoms and increased sweating. Such symptoms as well as sensory symptoms like hyposmia and pain are very frequently reported in PD and seem to occur early in the disease process. Braak proposed a sequential model of neuropathology in PD starting with affection of the olfactory bulb and the autonomic innervation of the heart and gut. Affection of SN is seen from Braak stage 3, and limbic and cortical structures are affected in the later stages of the disease. Currently, the evidence for sensory and autonomic involvement in PD is reviewed with special focus on the early phase of the disease. [source] Do axonal defects in tau and amyloid precursor protein transgenic animals model axonopathy in Alzheimer's disease?JOURNAL OF NEUROCHEMISTRY, Issue 4 2006Jürgen Götz Abstract The subcellular localization of organelles, mRNAs and proteins is particularly challenging in neurons. Owing to their extended morphology, with axons in humans exceeding a meter in length, in addition to which they are not renewed but persist for the entire lifespan, it is no surprise that neurons are highly vulnerable to any perturbation of their sophisticated transport machinery. There is emerging evidence that impaired transport is not only causative for a range of motor disorders, but possibly also for Alzheimer's disease (AD) and related neurodegenerative disorders. Support for this hypothesis comes from transgenic animal models. Overexpression of human tau and amyloid precursor protein (APP) in mice and flies models the key hallmark histopathological characteristics of AD, such as somatodendritic accumulation of phosphorylated forms of tau and ,-amyloid (A,) peptide-containing amyloid plaques, as well as axonopathy. The latter has also been demonstrated in mutant mice with altered levels of Alzheimer-associated genes, such as presenilin (PS). In A,-producing APP transgenic mice, axonopathy was observed before the onset of plaque formation and tau hyperphosphorylation. In human AD brain, an axonopathy was revealed for early but not late Braak stages. The overall picture is that key players in AD, such as tau, APP and PS, perturb axonal transport early on in AD, causing impaired synaptic plasticity and reducing survival rates. It will be challenging to determine the molecular mechanisms of these different axonopathies, as this might assist in the development of new therapeutic strategies. [source] A critical evaluation of the Braak staging scheme for Parkinson's disease,ANNALS OF NEUROLOGY, Issue 5 2008Robert E. Burke MD Braak and colleagues have proposed that, within the central nervous system, Parkinson's disease (PD) begins as a synucleinopathy in nondopaminergic structures of the lower brainstem or in the olfactory bulb. The brainstem synucleinopathy is postulated to progress rostrally to affect the substantia nigra and cause parkinsonism at a later stage of the disease. In the context of a diagnosis of PD, made from current clinical criteria, the pattern of lower brainstem involvement accompanying mesencephalic synucleinopathy is often observed. However, outside of that context, the patterns of synucleinopathy that Braak described are often not observed, particularly in dementia with Lewy bodies and when synucleinopathy occurs in the absence of neurological manifestations. The concept that lower brainstem synucleinopathy represents "early PD" rests on the supposition that it has a substantial likelihood of progressing within the human lifetime to involve the mesencephalon, and thereby cause the substantia nigra pathology and clinical parkinsonism that have heretofore defined the disease. However, the predictive validity of this concept is doubtful, based on numerous observations made in populations of aged individuals who, despite the absence of neurological signs, have brain synucleinopathy ranging up to Braak stages 4 to 6 at postmortem. Furthermore, there is no relation between Braak stage and the clinical severity of PD. We conclude that the relation between patterns of abnormal synuclein immunostaining in the human brain and the disease entity now recognized as PD remains to be determined. Ann Neurol 2008;64:485,491 [source] | |||||||||||||||||||