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These organelles accumulate during aging and are found predominantly in the catecholaminergic neurons of Substantia Nigra (SN) and Locus Coeruleus (LC), the main regions affected in Parkinson's disease (PD). NM serves a protective function by sequestering potentially toxic metals like Cu, Fe, and Al. However, NM released from degenerating neurons may lead to a cascade of events resulting in neuroinflammation and neurodegeneration. Therefore, elemental analysis of NM\u2010containing organelles presents a crucial step to understand aging and PD. In LC, such studies are limited because NM isolation requires large postmortem cohorts and analyses may be impaired by tissue processing. By integrating high resolution electron microscopy (EM), nano\u2010secondary ion mass spectrometry (nano\u2010SIMS), and energy dispersive X\u2010ray (EDX) microscpectroscopy, the elemental composition of intact NM\u2010containing organelles was analyzed in seven postmortem LC tissues. Chemical mapping with down to 5\u201310\u2009nm lateral resolution (EDX) fostered discrimination of structural composition (N, P, S, Cl) and metal storage (Al, Ca, Fe) across neurons and within individual NM\u2010containing organelle sub\u2010compartments (with diameters down to 0.2\u2009\u03bcm for lipid bodies) from the same sample. NM\u2010containing organelles were identified by an elemental fingerprint pattern. Metals accumulations were localized predominantly to the NM pigment compartment identified by its pheomelanin\u2010rich portion (S). This confirms NM's role in accumulating physiological as well as potentially toxic metal species. Moreover, semi\u2010quantitative analyses provided insights into inter\u2010 and intra\u2010subject NM metal accumulation, showing that S and Fe exhibited a positive aging trend. Hemispheric asymmetry was observed for Al, Ca, and Fe, with higher levels observed in NMs of the right brain hemisphere suggesting region\u2010specific accumulation that warrants further investigation to better understand aging\u2010related changes and the neuronal vulnerability of the LC in PD.<\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70531-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  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