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. 2021 Jun 22;18(13):6689. doi: 10.3390/ijerph18136689

Figure 1.

Figure 1

Distribution of misfolded proteins and neuropathological hallmarks in the brainstem and frontal cortex in Metropolitan Mexico City (MMC) individuals younger than 40 years [6,7,8,9,10,45,46]. The brainstem is an early target (motor, depression, arousal dysfunction and Autonomic Nervous System (ANS) dysfunction) [56,57,58,59,60,61] of misfolded proteins in Alzheimer, Parkinson and transactive response DNA-binding protein TDP-43 pathology in children and young adult residents in MMC [6]. (A) Brainstem pathology associated with RBD includes lesions in the pre-coeruleus, the sub-latero-dorsal nucleus, magnocellular nucleus, the locus coeruleus, degeneration in pedunculopontine nucleus, and corticothalamic circuits affecting the pathways that regulate REM sleep in the brainstem. Autonomic nervous system dysfunction, motor alterations, depression, and arousal mechanisms are impaired when the brainstem is involved in patients with dementia with Lewy bodies, Parkinson’s disease, multiple system atrophy and Alzheimer’s disease. (B) Positive hyperphosphorylated tau neurite in the mesencephalic reticular formation in an 11 m old baby (PHF-tau 8, Innogenetics, Belgium). (C) Substantia nigra pars compacta in a 17 year old male with + tau neurites (PHF-tau 8, brown DAB, counterstained with hematoxylin). (D) Pedunculopontine nucleus positive tau neurite in a 12 y old boy (PHF-tau 8, brown DAB). (E) Locus coeruleus neurons with + tau neurites in a 37 year old female (PHF-tau 8, brown DAB). (F) Midbrain, substantia nigra + tau tangles in neurons + neurites and plaques in a 40 year old male (PHF-tau 8, brown DAB). (G) Three-year-old boy + α-Syn neuron in the region of the medial lemniscus in the lower pons (α-Syn phosphorylated at Ser-129, LB 509, InVitrogen, Carlsbad, CA) (Red product). (H) Eleven y old female, lower medulla with numerous α-Syn positive neurons and neurites in the reticular formation region (LB509, red product). (I) Thirteen-year-old girl, substantia nigra pars compacta neurons + α-Syn (LB509, red product). (J) Fourteen-year-old male, pontine reticular formation several neurons with positive TDP-43 staining around mostly clear nuclei (TDP-43, mab 2G10, Roboscreen GmbH, Leipzig, Germany) (DAB, brown product). (K) Twenty-seven-year-old male, substantia nigra pars compacta neuron with neuromelanin degranulation and clearing of the nucleus (TDP-43, mab 2G10) (red product). (L) Frontal neuron tau positive in a 13-year-old female (PHF-tau 8, DAB brown product). (M) Eighteen-year-old male, frontal tau neurites cluster and neurons with Aβ perinuclear accumulation (PHF-tau 8, DAB brown product and beta amyloid 17–24 4G8 Covance, Emeryville, CA, USA, red product).