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- 2017
Embryonic development of selectively vulnerable neurons in Parkinson’s diseaseDOI: 10.1038/s41531-017-0022-4 Abstract: Clinical manifestations,225–228 brainstem nuclei, Lewy pathology and cell loss in Parkinson’s disease (PD). Nuclei with evidence cell loss in late PD (red) are distinguished from those with evidence for Lewy pathology alone (black). The dorsal motor nucleus of the vagus (10N)7, 8, 18, 229 and the intermediate reticular zone (IRt) of the medullary reticular formation18, 230 are among the earliest brainstem populations with Lewy pathology in PD (Braak stage 1). Located outside the brainstem, both olfactory bulb (OB) and the anterior olfactory nucleus (AON) may also show Lewy pathology at this early stage. Subsequently in Braak stage 2, Lewy pathology is found within three main nuclei: the locus coeruleus (LC),9, 10 the lower raphe nuclei (MoRa)18, 229 and the gigantically reticular nuclei (GiRt) of the medullary reticular formation.18 In Braak stage 3, together with the characteristic motor symptoms (extrapyramidal changes) and degeneration of the SNC,18, 27, 229 the upper raphe nuclei (PnRa), located in the pons, also presents with Lewy pathology. In Stage 3, multiple other nuclei of the midbrain tegmentum show Lewy pathology, including the pedunculopontine tegmental nucleus (PTg),18 the paranigral nucleus (PaN),18 the pigmented parabrachial nucleus (PBP)18 and the Edinger Wesphal nucleus (EW).18 However, only neuronal cell loss of the SNC is widely considered specific for PD (Supplementary 1). (Figure adapted from ref. 231 with brain ontology according to the Human brain reference atlas of the Allen Brain Atlas.142
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