The dorsal raphe nucleus shows phospho‐tau neurofibrillary changes before the transentorhinal region in Alzheimer's disease. A precocious onset?

Grinberg, Lea T.; Rüb, Udo; Ferretti, Renata E.L.; Nitrini, Ricardo; Farfel, José Marcelo; Polichiso, Lívia; Gierga, K.; Jacob‐Filho, Wilson; Heinsen, Helmut

doi:10.1111/j.1365-2990.2008.00997.x

Cited by 214 publications

(185 citation statements)

References 77 publications

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“…Although these regions are not typically atrophied in AD, there is a growing number of studies that report pathological changes in these regions (42)(43)(44)(45). The cerebellum and brainstem are also strongly connected to other cortical regions (46)(47)(48) and have been implicated as part of several intrinsic networks (22,49).…”

Section: Discussionmentioning

confidence: 99%

Intrinsic connectivity networks in healthy subjects explain clinical variability in Alzheimer’s disease

Lehmann

Madison

Ghosh

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

111

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Although previous studies have emphasized the vulnerability of the default mode network (DMN) in Alzheimer's disease (AD), little is known about the involvement of other functional networks and their relationship to clinical phenotype. To test whether clinicoanatomic heterogeneity in AD is driven by the involvement of specific networks, network connectivity was assessed in healthy subjects by seeding regions commonly and specifically atrophied in three clinical AD variants: early-onset AD (age at onset, <65 y; memory and executive deficits), logopenic variant primary progressive aphasia (language deficits), and posterior cortical atrophy (visuospatial deficits). Four-millimeter seed regions of interest were used to obtain intrinsic connectivity maps in 131 healthy controls (age, 65.5 ± 3.5 y). Atrophy patterns in independent cohorts of AD variant patients and their correspondence to connectivity networks in controls were also assessed. The connectivity maps of commonly atrophied regions of interest support posterior DMN and precuneus network involvement across AD variants, whereas seeding regions specifically atrophied in each AD variant revealed distinct, syndrome-specific connectivity patterns. Goodness-of-fit analysis of each connectivity map with network templates showed the highest correspondence between the early-onset AD seed connectivity map and anterior salience and right executive-control networks, the logopenic aphasia seed connectivity map and the language network, and the posterior cortical atrophy seed connectivity map and the higher visual network. Connectivity maps derived from controls matched regions commonly and specifically atrophied in the patients. Our findings indicate that the posterior DMN and precuneus network are commonly affected in AD variants, whereas syndrome-specific neurodegenerative patterns are driven by the involvement of specific networks outside the DMN. A lzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by extracellular accumulation of amyloid plaques, intracellular neurofibrillary tangles, and neuronal loss (1). Although most patients present with memory deficits, a significant minority of patients with AD present with nonamnestic syndromes (2, 3). Patients with nonfamilial early-onset AD (EOAD, defined as onset <65 y in most studies) often show heterogeneous cognitive deficits, including impairment in attention and executive functions (4, 5). Focal syndromes such as posterior cortical atrophy (PCA, characterized by predominant visuospatial and visuoperceptual deficits; ref. 6) and the logopenic variant of primary progressive aphasia [lvPPA, a progressive disorder of language (7,8)] are also most commonly caused by AD pathology. It has been suggested that up to 15% of patients with AD seen in dementia centers have nonamnestic presentations (2), and the importance of these syndromes is reflected in their inclusion in new diagnostic guidelines for AD (9, 10). The factors driving the clinicoanatomical heterogeneity in AD are not well understoo...

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Section: Discussionmentioning

confidence: 99%

Intrinsic connectivity networks in healthy subjects explain clinical variability in Alzheimer’s disease

Lehmann

Madison

Ghosh

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

111

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“…(Reproduced, with permission, from Seeley 2016, # 2016www.oup.com. ) phe in AD (Bondareff et al 1981;Grinberg et al 2009;Braak and Del Tredici 2012) and the dorsal motor nucleus of the vagus nerve in LBD (Braak et al 2003a). In LBD, the process may begin even more peripherally, in the olfactory mucosa and enteric nervous system.…”

Section: Mapping Neurodegenerationmentioning

confidence: 99%

Mapping Neurodegenerative Disease Onset and Progression

Seeley

2017

Cold Spring Harb Perspect Biol

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“…Moreover, although the pathological substrates of extrapyramidal signs remains debated, recent study on AD with parkinsonian features showed that motor impairment is the consequence of nigrostriatal pathology, leading authors to conclude that prominent subcortical involvement occur in these patients, a process apparently not related to the Braak stages (Horvath et al, 2014). Accordingly, signs of tau pathology in brain stem nuclei, becoming increasingly involved with AD progression has been proposed (Grinberg et al, 2009; Simic et al, 2009; Attems et al, 2012). More details on DA transmission system in both cortical and sub-cortical brain areas, which have never been observed before, have been recently discovered.…”

Section: Dopamine System In Alzheimer's Diseasementioning

confidence: 99%

â€œIs dopamine involved in Alzheimer's disease?â€

Martorana

Koch

2014

Front. Aging Neurosci.

229

184

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Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline and dementia. Recent advances indicate that AD pathogenesis appears more complex than its mere neuropathology. Changes in synaptic plasticity, neuronal disarray and cell death are pathways commonly recognized as pathogenic mechanisms of AD. It is thought that the altered metabolism of certain membrane proteins may lead to the production of amyloid (Aβ) oligomers that are characterized by an highly toxic effect on neurotransmission pathways, such as those mediated by Acetylcholine. The interaction of Aβ oligomers with these neurotansmitters systems would in turn induce cell dysfunction, neurotransmitters signaling imbalance and finally lead to the appearance of neurological signs. In this perspective, it is still debated how and if these mechanisms may also engage the dopaminergic system in AD. Recent experimental work revealed that the dopaminergic system may well be involved in the occurrence of cognitive decline, often being predictive of rapidly progressive forms of AD. However, a clear idea on the role of the dopamine system in AD is still missing. Here we review the more recent evidences supporting the notion that the dopaminergic dysfunction has a pathogenic role in cognitive decline symptoms of AD.

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The dorsal raphe nucleus shows phospho‐tau neurofibrillary changes before the transentorhinal region in Alzheimer's disease. A precocious onset?

Cited by 214 publications

References 77 publications

Intrinsic connectivity networks in healthy subjects explain clinical variability in Alzheimer’s disease

Intrinsic connectivity networks in healthy subjects explain clinical variability in Alzheimer’s disease

Mapping Neurodegenerative Disease Onset and Progression

â€œIs dopamine involved in Alzheimer's disease?â€

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The dorsal raphe nucleus shows phospho‐tau neurofibrillary changes before the transentorhinal region in Alzheimer's disease. A precocious onset?

Cited by 214 publications

References 77 publications

Intrinsic connectivity networks in healthy subjects explain clinical variability in Alzheimer’s disease

Intrinsic connectivity networks in healthy subjects explain clinical variability in Alzheimer’s disease

Mapping Neurodegenerative Disease Onset and Progression

â€œIs dopamine involved in Alzheimer's disease?â€

Contact Info

Product

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â€œIs dopamine involved in Alzheimer's disease?â€