Given the fact that they all appeared in the records at about the same time, and all but Alexander are known to have lived within the Laurel Fork watershed, within a few miles of each other, it can be assumed that they were all closely related. In fact, most genealogists identify them as brothers, sons of Thomas McSpadden who settled on Borden's Grant about 1740.  The five brothers are believed to have moved to the Holston by 1775, and may have come earlier, perhaps in the company of the extended Edmondson family, to whom some genealogists attach a marriage relation.
This is in part, confirmed by the pension applications of two of the brothers, Thomas and Archibald, that show that they were raised in Rockbridge County, and moved to the Holston settlement about 1775. Their applications go on to show that shortly after the end of the Revolution they moved to the Cumberland Settlement (Thomas) and to Jefferson County (Archibald). Samuel is also known to have moved to TN, at least late in life, as he appears in the household of a Thomas McSpadden (presumably his son) in Jefferson County in 1840. Only Moses McSpadden is thought to have remained in the area following the Revolution. The fate of Alexander McSpadden is, however, unknown, and he appears only once in the records of Southwest Virginia to show he was there at all.
A Moses McSpadden appears in the 1810 census of Washington County, and is appropriately aged to be the original settler of c1775. This Moses is successively replaced in later census'. A Moses McSpadden Jr. appears 1820 census record and is appropriately aged to be presumed to be the Moses who originally settled in the area. In 1830, Moses Jr. dissappears, being replaced by Thomas McSpadden, who then dissappears in the 1840 census replaced by a James W. McSpadden. Source:White, 1902:181 identifies a James Walker McSpadden son of Elizabeth Lyle Walker and Thomas McSpeddon of Rockbridge County, VA, and who was living in Alvarado in Washington County VA in 1896. This is presumably the James W. McSpadden of the 1840 census record.
 Thomas (1) of Rockbridge is said to have had several other sons besides those that came to SW VA: viz: Presumably, Thomas who married Elizabeth Lyle Walker is the son of one of those sons. That would make James W. a great grandson of Thomas (1). The presumption is that the line of Moses McSpadden has either left the area, or died out altogether, leaving the original property on Laurel Fork to cousin James W. McSpadden.